Allogeneic stem cell transplantation in the era of novel therapies for acute lymphoblastic leukaemia

array:24 ["pii" => "S238702061930275X" "issn" => "23870206" "doi" => "10.1016/j.medcle.2019.01.024" "estado" => "S300" "fechaPublicacion" => "2019-07-05" "aid" => "4763" "copyright" => "Elsevier España, S.L.U.. All rights reserved" "copyrightAnyo" => "2019" "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Med Clin. 2019;153:28-34" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0025775319300636" "issn" => "00257753" "doi" => "10.1016/j.medcli.2019.01.017" "estado" => "S300" "fechaPublicacion" => "2019-07-05" "aid" => "4763" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Med Clin. 2019;153:28-34" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 18 "formatos" => array:2 [ "HTML" => 12 "PDF" => 6 ] ] "es" => array:12 [ "idiomaDefecto" => true "cabecera" => "Revisión" "titulo" => "El trasplante alogénico de progenitores hematopoyéticos en la era de las nuevas terapias en la leucemia linfoblástica aguda" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "28" "paginaFinal" => "34" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Allogeneic stem cell transplantation in the era of novel therapies for acute lymphoblastic leukaemia" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Pere Barba, Izaskun Elorza" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Pere" "apellidos" => "Barba" ] 1 => array:2 [ "nombre" => "Izaskun" "apellidos" => "Elorza" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S238702061930275X" "doi" => "10.1016/j.medcle.2019.01.024" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S238702061930275X?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775319300636?idApp=UINPBA00004N" "url" => "/00257753/0000015300000001/v1_201906160629/S0025775319300636/v1_201906160629/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2387020619302761" "issn" => "23870206" "doi" => "10.1016/j.medcle.2019.06.006" "estado" => "S300" "fechaPublicacion" => "2019-07-05" "aid" => "4775" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Med Clin. 2019;153:35-40" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "Special article" "titulo" => "Directed to consumer genetic testing. Perspective from the Ethics commission of the Spanish Society for Human Genetics" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "35" "paginaFinal" => "40" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Pruebas genéticas de venta directa a los consumidores. Perspectiva de la Comisión de Ética de la Asociación Española de Genética Humana" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Teresa Pàmpols Ros, José Miguel García Sagredo, Antonio Pérez Aytés, Aranzazu Díaz de Bustamante" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Teresa" "apellidos" => "Pàmpols Ros" ] 1 => array:2 [ "nombre" => "José Miguel" "apellidos" => "García Sagredo" ] 2 => array:2 [ "nombre" => "Antonio" "apellidos" => "Pérez Aytés" ] 3 => array:2 [ "nombre" => "Aranzazu" "apellidos" => "Díaz de Bustamante" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775319301228" "doi" => "10.1016/j.medcli.2019.01.028" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775319301228?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020619302761?idApp=UINPBA00004N" "url" => "/23870206/0000015300000001/v1_201906260821/S2387020619302761/v1_201906260821/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2387020619302748" "issn" => "23870206" "doi" => "10.1016/j.medcle.2018.11.022" "estado" => "S300" "fechaPublicacion" => "2019-07-05" "aid" => "4715" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Med Clin. 2019;153:16-27" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "Review" "titulo" => "Seasonal influenza in Spain: Clinical and economic burden and vaccination programmes" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "16" "paginaFinal" => "27" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Gripe estacional en España: carga clínica y económica y programas de vacunación" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Adapted using data from the Spanish Influenza Surveillance System.<a class="elsevierStyleCrossRef" href="#bib0365">23</a>" "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1100 "Ancho" => 2503 "Tamanyo" => 95727 ] ] "descripcion" => array:1 [ "en" => "Distribution of influenza cases by age group, severe hospitalisations and deaths (2011–2017). SHCCI: serious hospitalised confirmed cases of influenza." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Alberto Pérez-Rubio, Leticia Platero, José María Eiros Bouza" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Alberto" "apellidos" => "Pérez-Rubio" ] 1 => array:2 [ "nombre" => "Leticia" "apellidos" => "Platero" ] 2 => array:2 [ "nombre" => "José María" "apellidos" => "Eiros Bouza" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775318307425" "doi" => "10.1016/j.medcli.2018.11.014" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775318307425?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020619302748?idApp=UINPBA00004N" "url" => "/23870206/0000015300000001/v1_201906260821/S2387020619302748/v1_201906260821/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "Review" "titulo" => "Allogeneic stem cell transplantation in the era of novel therapies for acute lymphoblastic leukaemia" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "28" "paginaFinal" => "34" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Pere Barba, Izaskun Elorza" "autores" => array:2 [ 0 => array:4 [ "nombre" => "Pere" "apellidos" => "Barba" "email" => array:1 [ 0 => "pbarba@vhio.net" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Izaskun" "apellidos" => "Elorza" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Hematología, Hospital Universitario Vall d’Hebron-Universitat Autónoma de Barcelona, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidad de Trasplante de Progenitores Hematopoyéticos Pediátrica, Hospital Universitari Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "El trasplante alogénico de progenitores hematopoyéticos en la era de las nuevas terapias en la leucemia linfoblástica aguda" ] ] "textoCompleto" => "IntroductionAllogeneic haematopoietic stem cell transplantation (allo-HSCT) offers patients who suffer from acute lymphoblastic leukaemia (ALL) with high risk of relapse better survival compared to conventional chemotherapy.<a class="elsevierStyleCrossRef" href="#bib0305">1</a> The optimisation of the transplant procedure and the greater facility to obtain compatible unrelated donors have meant that this therapy can today be offered to a greater number of patients, achieve higher disease-free survival (DFS) results and obtain lower transplant-related mortality (TRM) rates.<a class="elsevierStyleCrossRef" href="#bib0310">2</a>The field of ALL has undergone a real revolution in recent years. A greater biological knowledge of the disease has resulted in the appearance of numerous and innovative treatments, many of them based on immunotherapy.<a class="elsevierStyleCrossRef" href="#bib0315">3</a> These treatments include simple, conjugated or bispecific monoclonal antibodies and chimeric antigen receptor T-cells (CAR-T) for CD19 positive B-precursor ALL. While it seems evident that these new therapies will directly influence the treatment of ALL, indications and implementation of allo-HSCT and current uncertainties regarding how exactly that will occur, far exceeds what we do know for certain. On this basis, the purpose of this review is to summarise what we know about the role of haematopoietic stem cell transplantation (HSCT) in ALL and attempt to predict a possible direction on the positioning of this procedure in the near future, in both adult and paediatric patients.Transplantation indicationsThe indications for transplantation in adults differ significantly from those of paediatric patients. Because current indications for auto-HSCT in ALL are very residual, we will only discuss indications for allo-HSCT, except when explicitly mentioned. <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows current indications for allo-HSCT according to the European Bone Marrow Transplant (EBMT) group, while <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> contains indications from the PETHEMA group (for adult patients) and SHOP-PETHEMA 2013 (for paediatric patients), which are the cooperative groups in Spain.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Adult patientsDespite achieving complete remissions in up to 90% of patients, relapses in adult patients are common, affecting up to 50% of patients who do not receive allo-HSCT.<a class="elsevierStyleCrossRef" href="#bib0320">4</a> The prognosis of these relapsed patients is, to date, highly unfavourable.<a class="elsevierStyleCrossRef" href="#bib0325">5</a> This is why allo-HSCT remains a fundamental pillar in the treatment of ALL, either for first complete remission (CR1) or in patients with relapsed or refractory disease. Currently, ALL is the second most frequent indication for allo-HSCT in Europe and North America.<a class="elsevierStyleCrossRef" href="#bib0330">6</a>Allogeneic transplantation in first complete remissionSeveral groups analysed the role of allo-HSCT in ALL in first remission (CR1). Most prospective comparative studies were developed in the late twentieth century and were based on an genetic randomisation, so that only patients with a histocompatible donor received allo-HSCT in CR1.<a class="elsevierStyleCrossRefs" href="#bib0305">1,7</a> These studies showed that allo-HSCT was effective in reducing the risk of relapse, with greater benefit in standard risk ALL.<a class="elsevierStyleCrossRef" href="#bib0305">1</a> Evidence of the graft versus leukaemia effect in ALL has been reinforced in positive studies with infusion of donor lymphocytes and with the association of graft versus host disease (GvHD) development and a lower relapse rate.<a class="elsevierStyleCrossRef" href="#bib0340">8</a>The fact that a significant proportion of patients who did not receive an allo-HSCT in CR1 managed to achieve lasting remissions led several cooperative groups to improve the selection criteria of candidate patients. These studies, many based on treatment protocols inspired by paediatric regimens, found that patients with a good clearance of measurable residual disease (MRD) could achieve durable remissions during treatment (usually weeks 4–6 and weeks 16–18) without an allo-HSCT in CR1.<a class="elsevierStyleCrossRef" href="#bib0320">4</a> MRD can be determined through detection of leukaemic phenotype by flow cytometry and/or determination of immunoglobulin receptors/T cell by PCR techniques. The sensitivity of PCR techniques is higher than that of cytometry, although both have been shown to be feasible in clinical practice with high concordance between results.<a class="elsevierStyleCrossRef" href="#bib0345">9</a> On this basis, the current trend in most European cooperative groups is to reserve allo-HSCT in CR1 for at-risk patients, mainly those with poor clearance of MRD and/or with genetic criteria of poor prognosis at diagnosis, such as t(9;22) (q34q11), low hypodiploidy/almost aneuploidy and complex karyotype. At the molecular level, deletions of IKZF-1, rearrangements of KMT2A, alterations of CRLF-2 and of the RAS pathway (KRAS, NRAS and PTPN1), as well as Philadelphia-like subtype (in which some of the mentioned alterations are included) also suggest a bad prognosis.<a class="elsevierStyleCrossRef" href="#bib0350">10</a> In T-ALL, the absence of NOTCH-1 mutations and deletions of CDKN2A/B are also considered to have poor prognosis.<a class="elsevierStyleCrossRef" href="#bib0315">3</a> However, there is no consensus on whether these changes should mean, by themselves, indication for transplantation in Ph negative B-ALL.Classic clinical prognostic factors, such as leukocytosis or CNS infiltration, are not considered, by themselves, criteria to indicate allo-HSCT, since genetics and MRD are attributed a greater risk of relapse and, therefore, indication of HSCT.<a class="elsevierStyleCrossRef" href="#bib0355">11</a>Allogeneic transplantation in second complete remissionCurrently available data show that the prognosis of patients with relapsed ALL is very unfavourable. Although these patients are likely to achieve a second complete remission (CR2) (30–50%),<a class="elsevierStyleCrossRef" href="#bib0325">5</a> successive relapses are very common, which is why allo-HSCT is considered the only curative option for these patients after reaching a complete remission (CR).Paediatric patientsCurrent chemotherapy protocols offer paediatric patients with ALL an 80% chance of recovery.<a class="elsevierStyleCrossRef" href="#bib0360">12</a> The group of patients with high-risk, refractory or in early spinal relapse ALL (10% of all cases) have a DFS of less than 40% and are considered candidates for allo-HSCT.<a class="elsevierStyleCrossRef" href="#bib0365">13</a> High-risk patients are considered those who do not achieve remission with induction treatment, those who have detectable MRD after induction, and in whom a positive MRD is detected during treatment. MRD thresholds and the moment it is assessed vary according to the different study groups.<a class="elsevierStyleCrossRefs" href="#bib0360">12–14</a>Allogeneic transplantation in first complete remissionThe factors determining which patients are assigned to a more or less intense treatment group and indication of allo-HSCT in CR1 are clinical presentation, genetics and response to treatment.<a class="elsevierStyleCrossRef" href="#bib0360">12</a>The indication for transplantation in CR1 is reserved for patients who have responded poorly to treatment or a persistence of MRD. Study moments and MRD thresholds have been agreed on that predict a high risk of relapse and which are used for the indication of transplant. Slow responders, assessed at day seven and 14, can be rescued with intensive treatment in 70% of cases; however, those who do not achieve remission on day 28 have a 40% DFS, making them candidates for allo-HSCT in CR1.<a class="elsevierStyleCrossRef" href="#bib0365">13</a> In late moments of treatment, postconsolidation, patients with positive MRD are considered suitable candidates for allo-HSCT in CR1. Indication for allo-HSCT in CR1 is still being debated in patients with early T-cell precursor ALL, infants under six months with MLL gene rearrangements and patients with hypodiploidy karyotype, since it is disease with high resistance to chemotherapy.<a class="elsevierStyleCrossRef" href="#bib0375">15</a> A summary of the results of allo-HSCT in paediatric patients in CR1 are: an incidence of relapse rate of 10–20%, TRM 10–15% and DFS 65–80%.<a class="elsevierStyleCrossRef" href="#bib0380">16</a>Allogeneic transplantation in second complete remissionRelapse occurs in 15–20% of children who achieve remission after induction. The duration of the first remission influences the likelihood of long-term survival, such that early relapse (within six months after treatment) has less than a 40% survival rate with chemotherapy alone.<a class="elsevierStyleCrossRef" href="#bib0370">14</a> Extramedullary late and early relapses present good DFS results when chemotherapy is associated with local treatment. Allo-HSCT in CR2 mainly benefits children with early medullary relapse and those who, even when late, show poor response to treatment. The results of allo-HSCT in paediatric patients in CR2 are: post-HSCT relapse incidence rate 20–40%, TRM 15–25% and DFS 40–50%.<a class="elsevierStyleCrossRef" href="#bib0385">17</a> Children who receive transplants during successive remissions have very poor results even after receiving allo-HSCT, with a DFS of approximately 30%.<a class="elsevierStyleCrossRef" href="#bib0370">14</a>Conditioning regimesTotal body irradiation (TBI) at doses of 12Gy combined with cyclophosphamide at a dose of 60mg/kg/day (two days) is considered the standard conditioning regimen for this patient group. The TBI dose is fractionated into six sessions (two sessions per day), as a reduced toxicity is observed in the short- and long-term than when it is administered as a single dose. The survival benefit of radiotherapy in paediatric patients has been demonstrated<a class="elsevierStyleCrossRef" href="#bib0390">18</a>; however, and despite its wide use, evidence in adults is scarcer.<a class="elsevierStyleCrossRef" href="#bib0395">19</a> Some groups have evaluated other strategies with radiation therapy at lower doses (400cGy) or without radiation therapy, and their results have been satisfactory and comparable to standard conditioning.<a class="elsevierStyleCrossRefs" href="#bib0400">20,21</a> In paediatric patients younger than three, with a higher risk of secondary neoplasms and damage to neurological, endocrine and growth development, radiotherapy is replaced by intravenous busulfan, at a dose according to the patient's weight and preferably by plasma levels.<a class="elsevierStyleCrossRef" href="#bib0410">22</a> There is evidence that regimens without radiotherapy do not result in a worse control of the central nervous system disease compared to radiation therapy.<a class="elsevierStyleCrossRef" href="#bib0415">23</a>The introduction of reduced intensity (RI) regimens facilitated older patients and those with comorbidities’ access to HSCT. There are no randomised studies analysing the role of RI conditioning in ALL. Retrospective studies have shown that this approach is viable in patients with ALL who are not candidates for allo-HSCT with conventional conditioning.<a class="elsevierStyleCrossRefs" href="#bib0420">24,25</a> However, some (though not all) retrospective comparative studies have questioned the benefit of RI allo-HSCT in elderly patients, since the decrease in leukaemic relapse offered by allo-HSCT could not be compensated by the increase of the TRM.<a class="elsevierStyleCrossRef" href="#bib0430">26</a> The benefit of RI allo-HSCT in paediatric patients is limited; lower DFS than standard conditioning is offered,<a class="elsevierStyleCrossRef" href="#bib0435">27</a> but this is more an option for patients with accumulated morbidity and/or in second transplants.The introduction in recent years of new drugs in the chemotherapy regimen prior to HSCT should be considered when evaluating possible post-HSCT toxicities. Patients who have received rescue treatment with inotuzumab ozogamicin (InO) prior to transplantation have a higher risk of sinusoidal obstruction syndrome (SOS). In adults, the incidence can reach 11%.<a class="elsevierStyleCrossRef" href="#bib0440">28</a> The risk is especially high in patients receiving two alkylating agents during conditioning, such that avoiding this combination is prudent.<a class="elsevierStyleCrossRef" href="#bib0445">29</a> The use of defibrotide as an SOS prophylaxis has proven useful in paediatric patients at high risk,<a class="elsevierStyleCrossRef" href="#bib0450">30</a> and is currently being investigated in adult patients. The use of SOS prophylaxis in patients previously treated with InO could be considered while waiting for the results of ongoing clinical trials (<a href="ctgov:NCT02851407">NCT02851407</a>), although there is not yet any definitive evidence for it.Donor sources and typesAll progenitor sources (bone marrow [BM], peripheral blood [PB] and umbilical cord blood [UCB]) commonly used for other indications, as well as donor types, have proven to be useful in ALL.The preferred source for paediatric patients is BM, due to its lower incidence of chronic GvHD and long-term TRM compared to PB,<a class="elsevierStyleCrossRef" href="#bib0455">31</a> while in adults the most commonly used source is PB. In the paediatric field, UCB is a progenitor source for approximately 85–95% of patients and has the advantages of rapid accessibility, less restriction due to HLA compatibility, greater ethnic variability and adequate cellularity for paediatric weight.<a class="elsevierStyleCrossRef" href="#bib0460">32</a> Paediatric groups with UCB transplantation experience obtain results similar to BM<a class="elsevierStyleCrossRef" href="#bib0465">33</a> in ALL. UCB has also been used with promising results in adult patients,<a class="elsevierStyleCrossRef" href="#bib0470">34</a> although its use is currently decreasing<a class="elsevierStyleCrossRef" href="#bib0475">35</a> and being substituted by haploidentical transplantation.There is less experience with haploidentical transplantations, especially in a post-HSCT cyclophosphamide modality, but the published data seem satisfactory.<a class="elsevierStyleCrossRef" href="#bib0480">36</a> Experiences in haploidentical transplantation in paediatric patients is mainly based on ex vivo depletion platforms. Currently the depletion of TCR lymphocytes αβ allows infusion of haematopoietic progenitors, NK cells and T lymphocytes γδ with potent anti-infective and antileukaemic activity, reaching immune reconstitution earlier.<a class="elsevierStyleCrossRef" href="#bib0485">37</a>In summary, in light of the published data, the fact that indication for transplantation is for an ALL should not modify the choice of source or type of donor in a particular transplantation centre. Moreover, once the patient is in an optimal situation for the transplant, one should proceed with the best donor available at that time without delaying the transplantation to search for an ideal donor, since this delay could lead to relapse and in turn ineligibility for allo-HSCT.Philadelphia positive B-acute lymphoblastic leukaemiaPositive Philadelphia (Ph+) B-ALL is, also from an HSCT perspective, a peculiar entity. Because of its high risk of relapse in patients treated only with chemotherapy and tyrosine kinase inhibitors (TKI), the use of allo-HSCT in CR1 has been established. The majority of studies into adults have shown long-term survival greater than 40% in patients receiving allo-HSCT in CR1.<a class="elsevierStyleCrossRefs" href="#bib0490">38,39</a> The role of MRD positive prior to allo-HSCT is also important in B-ALL Ph+, and several studies have shown a worse prognosis in patients receiving allo-HSCT with positive MRD.<a class="elsevierStyleCrossRefs" href="#bib0500">40,41</a> In fact, some protocols include an intensification or change of TKI to intensify response prior to transplantation and deepen the clearance of the MRD.<a class="elsevierStyleCrossRef" href="#bib0490">38</a>Using TKI in post-HSCT, either as a universal treatment or as an anticipated treatment in the presence of detectable MRD, is recommended. However, there is no consensus regarding which of these two approaches is best, nor the choice of TKI or the duration of post-transplantation treatment. Importantly, TKIs have a non-negligible toxicity in post-HSCT,<a class="elsevierStyleCrossRef" href="#bib0510">42</a> especially in haematologic patients, so its administration is not recommended for at least the first 30days after transplantation.Evidence has recently appeared that some patients with Ph+ B-ALL (especially those with complete molecular remission) can achieve durable responses with maintenance using new TKI, preceded or not with auto-HSCT. In this regard, the French group demonstrated an OS of 80% in patients who had received a auto-HSCT and maintenance treatment with imatinib,<a class="elsevierStyleCrossRef" href="#bib0510">42</a> and the Italian group recently showed<a class="elsevierStyleCrossRef" href="#bib0515">43</a> promising long-term survival with chemotherapy and maintenance with ponatinib in elderly patients who were not candidates for allo-HSCT. It may be possible that new TKIs will mean that certain patients with Ph+ B-ALL will not have to undergo allo-HSCT in the future, but such approaches should only be considered under research conditions for now. Outside trail and research contexts, allo-HSCT remains the standard for adult patients in CR1.<a class="elsevierStyleCrossRef" href="#bib0490">38</a>In paediatric patients, Ph positive ALL accounts for only 5% of all ALL. The addition of TKI to conventional chemotherapy has allowed similar results to be achieved in patients with Ph negative and positive ALL,<a class="elsevierStyleCrossRef" href="#bib0520">44</a> such that the indication for allo-HSCT in CR1 is reserved for patients with poor response to first-line treatment.<a class="elsevierStyleCrossRef" href="#bib0525">45</a>In patients with relapsed or refractory Ph positive ALL, responses to new monoclonal antibodies such as blinatumomab or inotuzumab ozogamicin<a class="elsevierStyleCrossRefs" href="#bib0440">28,43</a> and with CAR T-cells<a class="elsevierStyleCrossRef" href="#bib0530">46</a> have been described. However, these therapies have not yet modified indication for HSCT in patients with Ph positive ALL and its use is limited to patients with post-transplantation relapse or in a research context, not candidates for transplantation.<a class="elsevierStyleCrossRef" href="#bib0535">47</a>Prognostic factors. The role of measurable residual diseaseIn patients with ALL who are candidates for allo-HSCT, the presence of MRD during the chemotherapy treatment prior to transplantation seems to have an impact on prognosis. Several groups<a class="elsevierStyleCrossRefs" href="#bib0355">11,48,49</a> (although not all)<a class="elsevierStyleCrossRef" href="#bib0550">50</a> have demonstrated the importance of this factor, either through flow cytometry or PCR techniques. Specifically, the Italian group demonstrated that patients with MRD>10−3 at week 16 and/or 22 had worse results after allo-HSCT, with a lower overall survival of 20% and an relapse incidence rate within six years of 64%.<a class="elsevierStyleCrossRef" href="#bib0355">11</a> Others, like the French group, did not observe these differences when they analysed MRD in an earlier period (week six).<a class="elsevierStyleCrossRef" href="#bib0550">50</a> However, in the French study this analysis was not included as a primary objective and performed only in a subset of patients (only 54 patients received allo-HSCT with MRD≥10−3), so these results should be interpreted with caution.In children, the impact of MRD prior to transplantation has been shown: a DFS of 20% was observed in patients with MRD>10−4 and of 74% in those with undetectable MRD by flow cytometry.<a class="elsevierStyleCrossRef" href="#bib0555">51</a> In this study by the EUROCORD group, the development of acute GvHD was associated with a lower risk of relapse, especially in the positive MRD pre-HSCT group. Given that the positive MRD pre-HSCT group had a lower DFS than those in the negative MRD group, the need to use pre-HSCT immunotherapy treatment was considered,<a class="elsevierStyleCrossRefs" href="#bib0560">52,53</a> which could reduce MRD and thus achieve better post-HSCT results. However, there is currently no evidence of whether this strategy is more effective than performing a direct allo-HSCT with detectable MRD.Regarding post-HSCT MRD, its usefulness as a predictive factor of relapse has been demonstrated. A study by the international BFM group showed that detection of MRD measured by flow cytometry after transplantation had an 87% success rate of predicting leukaemic relapse within two months.<a class="elsevierStyleCrossRef" href="#bib0570">54</a> The determination of chimerism is complementary to the study of post-transplant MRD and the absence of a complete donor chimaera has been associated with an increased risk of relapse.<a class="elsevierStyleCrossRef" href="#bib0575">55</a>Relapse after allogeneic transplantationIf paediatric patients who relapse after allo-HSCT go into remission and reach a second HSCT, they have an DFS of 30%.<a class="elsevierStyleCrossRef" href="#bib0580">56</a> As mentioned, the most important prognostic variable of DFS in a second HSCT is the duration of the first remission.<a class="elsevierStyleCrossRef" href="#bib0370">14</a> Other better DFS factors include the absence of MRD and not having presented GvHD during the first HSCT.Survival results after a second HSCT do not include the group of patients who do not reach a second HSCT. Approximately 30% of the patients who relapse pass away from refractory disease or due to the high toxicity associated with the aggressiveness of the rescue treatments, given that they are often patients with frequent morbidities and accumulated toxicity.Recent studies suggest that certain paediatric patients with early relapse post-HSCT, comorbidities or persistence of MRD would be candidates for immunotherapy before a second HSCT or even as replacement therapy for HSCT.<a class="elsevierStyleCrossRef" href="#bib0585">57</a> Clinical trials have shown that therapy with CAR-T anti-CD19 is very effective in children with CD19+ ALL who have relapsed after allo-HSCT, achieving complete remissions with a seemingly lower toxicity than conventional treatments, especially in patients with low tumour load.<a class="elsevierStyleCrossRef" href="#bib0565">53</a> Treatment with blinatumomab or InO for patients with post-HSCT relapse may be another alternative therapy to traditional chemotherapy.<a class="elsevierStyleCrossRefs" href="#bib0440">28,58</a>Future perspectives in the era of new treatmentsImmunotherapy is changing the way we treat ALL. Whether these advances will lead to changes in indications or even in conditioning treatments for these patients is still to be seen. Some recent studies have suggested<a class="elsevierStyleCrossRef" href="#bib0530">46</a> that certain therapies, especially CAR-T, might replace HSCT and lead to a decrease in transplantations to treat this disease. In this sense, long-lasting remissions have been observed in patients with relapsed ALL after administering CAR T-cells, even without a subsequent allo-HSCT.<a class="elsevierStyleCrossRef" href="#bib0595">59</a> Conversely, these new tools may improve the treatment of patients who are refractory or relapsing and allow allo-HSCT to treat patients who are unable to be treated with HSCT. In addition, CAR-T can clarify the presence of MRD with a much lower toxicity than conventional chemotherapy and treat the patient with allo-HSCT and with lower morbidities and, therefore, lower toxicity.The new monoclonal antibodies, such as blinatumomab or InO, among others, have shown the ability to induce complete quality responses, with very low or even undetectable MRD, in a percentage of patients significantly higher than conventional chemotherapy,<a class="elsevierStyleCrossRefs" href="#bib0590">58,60</a> although these responses are usually short-lived and a subsequent allo-HSCT is required. Whether these and other monoclonal antibodies in first-line treatment can reduce relapses to initial treatment and thus decrease the number of patient candidates for transplantation is yet to be confirmed. Finally, it is important to note that most treatments based on immunotherapy today are only effective against B-lineage ALL. This is why there are not as many prospects for changes in HSCT indication for T-ALL, at least in the short term.ConclusionsDespite all the advances in the management of patients with ALL, allo-HSCT remains a fundamental pillar of treatment. HSCT achieves lasting responses in patients with clinical and biological characteristics of poor prognosis and in patients with relapse or refractory disease. The continuous optimisation of the procedure, improvements in the selection of transplantation candidates, the greater availability of donors at the optimal time (thanks, mainly, to haploidentical transplants) and the use of therapies to prevent relapse of the underlying disease, should all facilitate further improvement of the prognosis of these patients beyond what we have already seen in the last decades in paediatric patients and, to a lesser extent, in adult patients. Patients with positive MRD prior to transplantation may be candidates for immunotherapy with CAR-T or monoclonal antibodies with the objective of improving DFS. Another group that can benefit from these therapies is those patients who relapse after an allo-HSCT, especially those that present early relapse and/or associate morbidities and/or refractory disease. The intention of immunotherapy in these cases is to control the disease with as little toxicity as possible, and in some cases to achieve prolonged remissions, when faced with the impossibility of performing a second HSCT. And the possibility that these therapies in themselves may be curative for certain patients is currently under study.FundingPB received funding from the Carlos III Institute of Health FIS16/01433 project and a PERIS 2018–2020 grant from the Generalitat de Catalunya (BDNS357800).Conflict of interestPB has received funding for advice and/or travel from Amgen, Pfizer, Novartis, Jazz Pharmaceuticals and Shire, without affecting the content of this review. IE declares no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:16 [ 0 => array:3 [ "identificador" => "xres1211919" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1127989" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1211918" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1127990" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Transplantation indications" "secciones" => array:2 [ 0 => array:3 [ "identificador" => "sec0015" "titulo" => "Adult patients" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Allogeneic transplantation in first complete remission" ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Allogeneic transplantation in second complete remission" ] ] ] 1 => array:3 [ "identificador" => "sec0030" "titulo" => "Paediatric patients" "secciones" => array:1 [ 0 => array:3 [ "identificador" => "sec0035" "titulo" => "Allogeneic transplantation in first complete remission" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Allogeneic transplantation in second complete remission" ] ] ] ] ] ] ] 6 => array:2 [ "identificador" => "sec0045" "titulo" => "Conditioning regimes" ] 7 => array:2 [ "identificador" => "sec0050" "titulo" => "Donor sources and types" ] 8 => array:2 [ "identificador" => "sec0055" "titulo" => "Philadelphia positive B-acute lymphoblastic leukaemia" ] 9 => array:2 [ "identificador" => "sec0060" "titulo" => "Prognostic factors. The role of measurable residual disease" ] 10 => array:2 [ "identificador" => "sec0065" "titulo" => "Relapse after allogeneic transplantation" ] 11 => array:2 [ "identificador" => "sec0070" "titulo" => "Future perspectives in the era of new treatments" ] 12 => array:2 [ "identificador" => "sec0075" "titulo" => "Conclusions" ] 13 => array:2 [ "identificador" => "sec0080" "titulo" => "Funding" ] 14 => array:2 [ "identificador" => "sec0085" "titulo" => "Conflict of interest" ] 15 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-07-31" "fechaAceptado" => "2019-01-09" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1127989" "palabras" => array:5 [ 0 => "Allogeneic transplantation" 1 => "Acute lymphoblastic leukaemia" 2 => "Immunotherapy" 3 => "Monoclonal antibodies" 4 => "CAR-T" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1127990" "palabras" => array:5 [ 0 => "Trasplante alogénico" 1 => "Leucemia linfoblástica aguda" 2 => "Inmunoterapia" 3 => "Anticuerpos monoclonales" 4 => "CAR-T" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Immunotherapy is changing the treatment of acute lymphoblastic leukaemia (ALL) in adults and children. However, regardless of these new therapies, allogeneic hematopoietic cell transplantation (allo-HCT) still play a key role in the treatment of ALL, although it is uncertain how these new therapies will impact on the transplant procedure and indications. This article reviews the indications of allo-HCT for children and adults diagnosed with ALL, the different sources and conditioning regimens for transplantation as well as the role of measurable residual diseases pre- and post-HCT in the era of the new therapies for ALL." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "La inmunoterapia está cambiando profundamente el tratamiento de la leucemia linfoblástica aguda (LLA) infantil y del adulto. Sin embargo, a pesar de todos los avances, el trasplante alogénico de progenitores hematopoyéticos (alo-TPH) sigue siendo un pilar fundamental en su tratamiento. Cómo van a modificar estas nuevas terapias la indicación y el procedimiento de trasplante, resulta todavía incierto. En el presente artículo se discuten las indicaciones de TPH en la LLA infantil y del adulto, las posibles fuentes de donantes y acondicionamiento, así como el papel de la enfermedad residual medible en el contexto de la nueva era de tratamientos en el campo de la LLA." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Barba P, Elorza I. El trasplante alogénico de progenitores hematopoyéticos en la era de las nuevas terapias en la leucemia linfoblástica aguda. Med Clin (Barc). 2019;153:28–34." ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Indication \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HLA 10/10<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Alternative donor<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Observations \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Adult patients</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ph negative ALL in CR1, good clearance of MRD and no genetic factors of poor prognosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Not recommended \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Not recommended \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ph negative ALL in CR1, good clearance of MRD and with genetic factors of poor prognosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Clinical option \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Clinical option \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">In the case of alternative donors, consider the risk of theoretical TRM \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ph negative ALL in CR1, slow clearance of MRD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Standard \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Standard \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Try to perform HSCT in negative MRD or at least as low as possible \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ph negative ALL in incipient relapse \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Standard \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Standard \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">As far as possible, perform some non-toxic treatment to proceed to HSCT in MRD negative \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ph negative ALL in CR2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Standard \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Standard \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ph negative ALL in refractoriness \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Not recommended \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Not recommended \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ph positive ALL in CR1 without detectable MRD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Standard \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Standard \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">In patients without donor or at high risk of TRM, ABSCT and subsequent maintenance with TKI can be considered. Ideally in a clinical trial \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ph positive ALL in CR1 with detectable MRD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Clinical option \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Clinical option \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">If possible, change TKI to deepen the response prior to HSCT \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ph positive ALL in CR2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Clinical option \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Clinical option \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Standard, if for some reason HSCT was not performed in CR1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ph positive or negative ALL in refractoriness \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Not recommended \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Not recommended \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Paediatric patients</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Low-risk ALL<a class="elsevierStyleCrossRef" href="#tblfn0015">c</a> in CR1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Not recommended \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Not recommended \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Good results with chemotherapy. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">High risk<a class="elsevierStyleCrossRef" href="#tblfn0015">c</a> ALL in CR1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Standard \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Clinical option \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Use of all sources and donors. Use the one that is available at the optimum time for the transplant according to the centre's protocol \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALL in CR2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Standard \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Clinical option \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Try to perform HSCT in negative MRD or at least as low as possible \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALL in CR >2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Standard \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Clinical option \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">As far as possible, perform some non-toxic treatment to proceed to HSCT in MRD negative \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2068976.png" ] ] ] "notaPie" => array:3 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Family or unrelated donor." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "Alternative donor: HLA 9/10, haploidentical or umbilical cord blood." ] 2 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "c" "nota" => "Categories based on the number of leukocytes at diagnosis, cytogenetics, molecular markers and time to remission. MRD: measurable residual disease; HLA: human leucocyte antigen; TKI: tyrosine kinase inhibitors; ALL: acute lymphoblastic leukaemia; TRM: transplant related mortality; Ph: Philadelphia; CR: complete response; ABSCT: autologous peripheral blood stem cell transplant; HSCT: hematopoietic stem cell transplantation. Authors’ recommendations based on EBMT transplantation indications (Sureda et al. Bone Marrow Transplantation; 2015)." ] ] ] "descripcion" => array:1 [ "en" => "Indications of allogeneic transplantation in adult acute lymphoblastic leukaemia depending on the clinical situation according to the European Society for Bone and Marrow Transplantation (EBMT)." ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "tablatextoimagen" => array:2 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Adult patients \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">First referral \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No cytological complete remission after induction (day +28) or complete remission with MRD>10−3 measured by flow cytometry \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MRD>10−4 measured by flow cytometry after block B3 consolidation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Emergence of positive MRD at some point in the follow-up beyond block B3 consolidation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Second referral \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">All patients who are transplant candidates<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2068975.png" ] ] 1 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Paediatric patients \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">First referral \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No cytomorphologic complete remission after induction A (day +33), confirmed by flow cytometry \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MRD>10−2 after induction A (day +33) and MRD>10−3 at day +78 (prior to consolidation or at block HR-1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">At t(4;11) with MRD>10−3 at day +78 (prior to block HR-1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">In hypodiploidy (<44 chromosomes) with MRD>10−3 at day +78 (prior to block HR-1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">In T-ALL with poor response to prednisone and MRD>10−3 at day +78 (prior to block HR-1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">In HR patients if MRD is persistently positive>10−4 (after third block HR-3) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Second referral \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Relapse of ALL phenotype T \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Early medullary relapse of precursor-B ALL (<36months from diagnosis) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Early extramedullary relapse of precursor-B ALL (<18months from diagnosis) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Late relapse of precursor-B ALL with poor response to chemotherapy \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2068974.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "a" "nota" => "This is a recommendation. The protocol does not specifically include patients in CR2. HR: high risk; MRD: measurable residual disease; ALL: acute lymphoblastic leukaemia." ] ] ] "descripcion" => array:1 [ "en" => "Indications for allogeneic transplantation in acute lymphoblastic leukaemia in high-risk adult (PETHEMA AR-2011 Protocol) and paediatric patients (LAL/SHOP-Pethema 2013 Protocol)." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:60 [ 0 => array:3 [ "identificador" => "bib0305" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.H. Goldstone" 1 => "S.M. Richards" 2 => "H.M. Lazarus" 3 => "M.S. Tallman" 4 => "G. Buck" 5 => "A.K. Fielding" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2007-10-116582" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2008" "volumen" => "111" "paginaInicial" => "1827" "paginaFinal" => "1833" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18048644" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0310" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reduced mortality after allogeneic hematopoietic-cell transplantation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T.A. Gooley" 1 => "J.W. Chien" 2 => "S.A. Pergam" 3 => "S. Hingorani" 4 => "M.L. Sorror" 5 => "M. Boeckh" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1004383" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2010" "volumen" => "363" "paginaInicial" => "2091" "paginaFinal" => "2101" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21105791" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0315" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Acute lymphoblastic leukemia in adults: steps ahead" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.M. Ribera" 1 => "S. Vives" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Med Clin (Barc)" "fecha" => "2017" "volumen" => "149" "paginaInicial" => "119" "paginaFinal" => "121" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0320" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatment of high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in adolescents and adults according to early cytologic response and minimal residual disease after consolidation assessed by flow cytometry: final results of the PETHEMA ALL-AR-03 trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.M. Ribera" 1 => "A. Oriol" 2 => "M. Morgades" 3 => "P. Montesinos" 4 => "J. Sarrà" 5 => "J. González-Campos" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2013.52.2425" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2014" "volumen" => "32" "paginaInicial" => "1595" "paginaFinal" => "1604" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24752047" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0325" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA Study Group" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Oriol" 1 => "S. Vives" 2 => "J.M. Hernández-Rivas" 3 => "M. Tormo" 4 => "I. Heras" 5 => "C. Rivas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3324/haematol.2009.014274" "Revista" => array:6 [ "tituloSerie" => "Haematologica" "fecha" => "2010" "volumen" => "95" "paginaInicial" => "589" "paginaFinal" => "596" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20145276" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0330" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Use of haploidentical stem cell transplantation continues to increase: the 2015 European Society for Blood and Marrow Transplant activity survey report" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.R. Passweg" 1 => "H. Baldomero" 2 => "P. Bader" 3 => "C. Bonini" 4 => "R.F. Duarte" 5 => "C. Dufour" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/bmt.2017.34" "Revista" => array:6 [ "tituloSerie" => "Bone Marrow Transplant" "fecha" => "2017" "volumen" => "52" "paginaInicial" => "811" "paginaFinal" => "817" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28287639" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0335" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Myeloablative allogeneic versus autologous stem cell transplantation in adult patients with acute lymphoblastic leukemia in first remission: a prospective sibling donor versus no-donor comparison" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.J. Cornelissen" 1 => "B. van der Holt" 2 => "G.E. Verhoef" 3 => "M.B. van’t Veer" 4 => "M.H. van Oers" 5 => "H.C. Schouten" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2008-07-168625" "Revista" => array:7 [ "tituloSerie" => "Blood" "fecha" => "2009" "volumen" => "113" "paginaInicial" => "1375" "paginaFinal" => "1382" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18988865" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0939475314001732" "estado" => "S300" "issn" => "09394753" ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0340" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "NIH-defined graft-versus-host disease and evidence for a potent graft-versus-leukemia effect in patients with acute lymphoblastic leukemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T.H. Terwey" 1 => "T.M. le Duc" 2 => "P.G. Hemmati" 3 => "P. le Coutre" 4 => "M. Nagy" 5 => "P. Martus" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/annonc/mds615" "Revista" => array:6 [ "tituloSerie" => "Ann Oncol" "fecha" => "2013" "volumen" => "24" "paginaInicial" => "1363" "paginaFinal" => "1370" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23247660" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0345" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Flow cytometry and IG/TCR quantitative PCR for minimal residual disease quantitation in acute lymphoblastic leukemia: a French multicenter prospective study on behalf of the FRALLE, EORTC and GRAALL" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Garand" 1 => "K. Beldjord" 2 => "H. Cavé" 3 => "C. Fossat" 4 => "I. Arnoux" 5 => "V. Asnafi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/leu.2012.234" "Revista" => array:6 [ "tituloSerie" => "Leukemia" "fecha" => "2013" "volumen" => "27" "paginaInicial" => "370" "paginaFinal" => "376" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23070018" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0350" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genetics and prognosis of ALL in children vs adults" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "K.G. Roberts" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/asheducation-2018.1.137" "Revista" => array:6 [ "tituloSerie" => "Hematology Am Soc Hematol Educ Program" "fecha" => "2018" "volumen" => "2018" "paginaInicial" => "137" "paginaFinal" => "145" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30504302" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0355" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Different molecular levels of post-induction minimal residual disease may predict hematopoietic stem cell transplantation outcome in adult Philadelphia-negative acute lymphoblastic leukemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Bassan" 1 => "O. Spinelli" 2 => "E. Oldani" 3 => "T. Intermesoli" 4 => "M. Tosi" 5 => "B. Peruta" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/bcj.2014.48" "Revista" => array:5 [ "tituloSerie" => "Blood Cancer J" "fecha" => "2014" "volumen" => "4" "paginaInicial" => "e225" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25014772" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0360" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Risk- and response-based classification of childhood B-precursor acute lymphoblastic leukemia: a combined analysis of prognostic markers from the Pediatric Oncology Group (POG) and Children's Cancer Group (CCG)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K.R. Schultz" 1 => "D.J. Pullen" 2 => "H.N. Sather" 3 => "J.J. Shuster" 4 => "M. Devidas" 5 => "M.J. Borowitz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2006-01-024729" "Revista" => array:7 [ "tituloSerie" => "Blood" "fecha" => "2007" "volumen" => "109" "paginaInicial" => "926" "paginaFinal" => "935" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17003380" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S014067361631460X" "estado" => "S300" "issn" => "01406736" ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0365" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Outcomes after induction failure in childhood acute lymphoblastic leukemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Schrappe" 1 => "S.P. Hunger" 2 => "C.H. Pui" 3 => "V. Saha" 4 => "P.S. Gaynon" 5 => "A. Baruchel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1110169" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2012" "volumen" => "366" "paginaInicial" => "1371" "paginaFinal" => "1381" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22494120" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0370" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Outcome of children with multiply relapsed B-cell acute lymphoblastic leukemia: a therapeutic advances in childhood leukemia & lymphoma study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "W. Sun" 1 => "J. Malvar" 2 => "R. Sposto" 3 => "A. Verma" 4 => "J.J. Wilkes" 5 => "R. Dennis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/s41375-018-0094-0" "Revista" => array:2 [ "tituloSerie" => "Leukemia" "fecha" => "2018" ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0375" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Improved outcome with hematopoietic stem cell transplantation in a poor prognostic subgroup of infants with mixed-lineage-leukemia (MLL)-rearranged acute lymphoblastic leukemia: results from the Interfant-99 Study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. Mann" 1 => "A. Attarbaschi" 2 => "M. Schrappe" 3 => "P. de Lorenzo" 4 => "C. Peters" 5 => "I. Hann" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2010-03-273532" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2010" "volumen" => "116" "paginaInicial" => "2644" "paginaFinal" => "2650" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20592248" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0380" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Stem-cell transplantation in children with acute lymphoblastic leukemia: a prospective international multicenter trial comparing sibling donors with matched unrelated donors—the ALL-SCT-BFM-2003 trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Peters" 1 => "M. Schrappe" 2 => "A. von Stackelberg" 3 => "A. Schrauder" 4 => "P. Bader" 5 => "W. Ebell" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2014.58.9747" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2015" "volumen" => "33" "paginaInicial" => "1265" "paginaFinal" => "1274" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25753432" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0385" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Outcomes after HLA-matched sibling transplantation or chemotherapy in children with B-precursor acute lymphoblastic leukemia in a second remission: a collaborative study of the Children's Oncology Group and the Center for International Blood and Marrow Transplant Research" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Eapen" 1 => "E. Raetz" 2 => "M.J. Zhang" 3 => "C. Muehlenbein" 4 => "M. Devidas" 5 => "T. Abshire" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2005-12-4942" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2006" "volumen" => "107" "paginaInicial" => "4961" "paginaFinal" => "4967" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16493003" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0390" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Factors associated with long-term risk of relapse after unrelated cord blood transplantation in children with acute lymphoblastic leukemia in remission" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K.M. Page" 1 => "M. Labopin" 2 => "A. Ruggeri" 3 => "G. Michel" 4 => "C. Diaz de Heredia" 5 => "T. O’Brien" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.bbmt.2017.04.015" "Revista" => array:6 [ "tituloSerie" => "Biol Blood Marrow Transplant" "fecha" => "2017" "volumen" => "23" "paginaInicial" => "1350" "paginaFinal" => "1358" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28438676" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0395" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A comparison of cyclophosphamide and total body irradiation with etoposide and total body irradiation as conditioning regimens for patients undergoing sibling allografting for acute lymphoblastic leukemia in first or second complete remission" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.I. Marks" 1 => "S.J. Forman" 2 => "K.G. Blume" 3 => "W.S. Pérez" 4 => "D.J. Weisdorf" 5 => "A. Keating" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.bbmt.2005.12.029" "Revista" => array:6 [ "tituloSerie" => "Biol Blood Marrow Transplant" "fecha" => "2006" "volumen" => "12" "paginaInicial" => "438" "paginaFinal" => "453" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16545728" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0400" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Allogeneic stem cell transplantation after conditioning with treosulfan, etoposide and cyclophosphamide for patients with ALL: a phase II-study on behalf of the German Cooperative Transplant Study Group and ALL Study Group (GMALL)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Kröger" 1 => "M. Bornhäuser" 2 => "M. Stelljes" 3 => "U. Pichlmeier" 4 => "R. Trenschel" 5 => "C. Schmid" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/bmt.2015.202" "Revista" => array:6 [ "tituloSerie" => "Bone Marrow Transplant" "fecha" => "2015" "volumen" => "50" "paginaInicial" => "1503" "paginaFinal" => "1507" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26367236" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0405" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Intravenous busulfan compared with total body irradiation pretransplant conditioning for adults with acute lymphoblastic leukemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Kebriaei" 1 => "C. Anasetti" 2 => "M.J. Zhang" 3 => "H.L. Wang" 4 => "I. Aldoss" 5 => "M. de Lima" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.bbmt.2017.11.025" "Revista" => array:6 [ "tituloSerie" => "Biol Blood Marrow Transplant" "fecha" => "2018" "volumen" => "24" "paginaInicial" => "726" "paginaFinal" => "733" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29197676" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0410" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Risk factors for subsequent central nervous system tumors in pediatric allogeneic hematopoietic cell transplant: a study from the center for international blood and marrow transplant research (CIBMTR)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Gabriel" 1 => "B.E. Shaw" 2 => "R. Brazauskas" 3 => "M. Chen" 4 => "D.A. Margolis" 5 => "H. Sengelov" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.bbmt.2017.04.004" "Revista" => array:6 [ "tituloSerie" => "Biol Blood Marrow Transplant" "fecha" => "2017" "volumen" => "23" "paginaInicial" => "1320" "paginaFinal" => "1326" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28411175" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0415" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Outcome analysis of pediatric patients with acute lymphoblastic leukemia treated with total body irradiation-free allogeneic hematopoietic stem cell transplantation: comparison of patients with and without central nervous system involvement" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A.A. Hamidieh" 1 => "S.M. Monzavi" 2 => "M. Kaboutari" 3 => "M. Behfar" 4 => "M. Esfandbod" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.bbmt.2017.08.036" "Revista" => array:6 [ "tituloSerie" => "Biol Blood Marrow Transplant" "fecha" => "2017" "volumen" => "23" "paginaInicial" => "2110" "paginaFinal" => "2117" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28870778" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0420" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reduced-intensity versus conventional myeloablative conditioning allogeneic stem cell transplantation for patients with acute lymphoblastic leukemia: a retrospective study from the European Group for Blood and Marrow Transplantation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Mohty" 1 => "M. Labopin" 2 => "L. Volin" 3 => "A. Gratwohl" 4 => "G. Socié" 5 => "J. Esteve" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2010-02-266551" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2010" "volumen" => "116" "paginaInicial" => "4439" "paginaFinal" => "4443" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20716774" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0425" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The outcome of full-intensity and reduced-intensity conditioning matched sibling or unrelated donor transplantation in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first and second complete remission" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.I. Marks" 1 => "T. Wang" 2 => "W.S. Pérez" 3 => "J.H. Antin" 4 => "E. Copelan" 5 => "R.P. Gale" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2010-01-264077" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2010" "volumen" => "116" "paginaInicial" => "366" "paginaFinal" => "374" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20404137" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0430" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Impact of transplant eligibility and availability of a human leukocyte antigen-identical matched related donor on outcome of older patients with acute lymphoblastic leukemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Barba" 1 => "R. Martino" 2 => "D. Martinez-Cuadron" 3 => "G. Olga" 4 => "A. Esquirol" 5 => "C. Gil-Cortés" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3109/10428194.2015.1014365" "Revista" => array:6 [ "tituloSerie" => "Leuk Lymphoma" "fecha" => "2015" "volumen" => "56" "paginaInicial" => "2812" "paginaFinal" => "2818" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25686647" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0435" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reduced-intensity conditioning regimens for allogeneic transplantation in children with acute lymphoblastic leukemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.R. Verneris" 1 => "M. Eapen" 2 => "R. Duerst" 3 => "P.A. Carpenter" 4 => "M.J. Burke" 5 => "B.V. Afanasyev" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.bbmt.2010.03.009" "Revista" => array:6 [ "tituloSerie" => "Biol Blood Marrow Transplant" "fecha" => "2010" "volumen" => "16" "paginaInicial" => "1237" "paginaFinal" => "1244" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20302960" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0440" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H.M. Kantarjian" 1 => "D.J. DeAngelo" 2 => "M. Stelljes" 3 => "G. Martinelli" 4 => "M. Liedtke" 5 => "W. Stock" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1509277" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2016" "volumen" => "375" "paginaInicial" => "740" "paginaFinal" => "753" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27292104" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0445" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatic adverse event profile of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukaemia: results from the open-label, randomised, phase 3 INO-VATE study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H.M. Kantarjian" 1 => "D.J. DeAngelo" 2 => "A.S. Advani" 3 => "M. Stelljes" 4 => "P. Kebriaei" 5 => "R.D. Cassaday" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S2352-3026(17)30103-5" "Revista" => array:6 [ "tituloSerie" => "Lancet Haematol" "fecha" => "2017" "volumen" => "4" "paginaInicial" => "e387" "paginaFinal" => "e398" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28687420" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0450" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Defibrotide for prophylaxis of hepatic veno-occlusive disease in paediatric haemopoietic stem-cell transplantation: an open-label, phase 3, randomised controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Corbacioglu" 1 => "S. Cesaro" 2 => "M. Faraci" 3 => "D. Valteau-Couanet" 4 => "B. Gruhn" 5 => "A. Rovelli" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(11)61938-7" "Revista" => array:7 [ "tituloSerie" => "Lancet" "fecha" => "2012" "volumen" => "379" "paginaInicial" => "1301" "paginaFinal" => "1309" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22364685" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S1933287417300648" "estado" => "S300" "issn" => "19332874" ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0455" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "More chronic GvHD and non-relapse mortality after peripheral blood stem cell compared with bone marrow in hematopoietic transplantation for paediatric acute lymphoblastic leukemia: a retrospective study on behalf of the EBMT Paediatric Diseases Working Party" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Simonin" 1 => "A. Dalissier" 2 => "M. Labopin" 3 => "A. Willasch" 4 => "M. Zecca" 5 => "A. Mouhab" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/bmt.2017.66" "Revista" => array:6 [ "tituloSerie" => "Bone Marrow Transplant" "fecha" => "2017" "volumen" => "52" "paginaInicial" => "1071" "paginaFinal" => "1073" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28394370" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0460" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cord blood transplantation: state of the art" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "E. Gluckman" 1 => "V. Rocha" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3324/haematol.2009.005694" "Revista" => array:7 [ "tituloSerie" => "Haematologica" "fecha" => "2009" "volumen" => "94" "paginaInicial" => "451" "paginaFinal" => "454" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19336748" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0140673607617784" "estado" => "S300" "issn" => "01406736" ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0465" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Eapen" 1 => "P. Rubinstein" 2 => "M.J. Zhang" 3 => "C. Stevens" 4 => "J. Kurtzberg" 5 => "A. Scaradavou" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(07)60915-5" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2007" "volumen" => "369" "paginaInicial" => "1947" "paginaFinal" => "1954" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17560447" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0470" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Umbilical cord blood transplantation from unrelated donors in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.L. Piñana" 1 => "J. Sanz" 2 => "A. Picardi" 3 => "C. Ferrá" 4 => "R. Martino" 5 => "P. Barba" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3324/haematol.2013.091009" "Revista" => array:6 [ "tituloSerie" => "Haematologica" "fecha" => "2014" "volumen" => "99" "paginaInicial" => "378" "paginaFinal" => "384" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24097633" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0475" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Is the use of unrelated donor transplantation leveling off in Europe? The 2016 European Society for Blood and Marrow Transplant activity survey report" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.R. Passweg" 1 => "H. Baldomero" 2 => "P. Bader" 3 => "G.W. Basak" 4 => "C. Bonini" 5 => "R. Duarte" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/s41409-018-0153-1" "Revista" => array:6 [ "tituloSerie" => "Bone Marrow Transplant" "fecha" => "2018" "volumen" => "53" "paginaInicial" => "1139" "paginaFinal" => "1148" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29540849" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0480" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Haploidentical transplantation with post-transplantation cyclophosphamide for high-risk acute lymphoblastic leukemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.A. Srour" 1 => "D.R. Milton" 2 => "A. Bashey" 3 => "A. Karduss-Urueta" 4 => "M.M. al Malki" 5 => "R. Romee" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.bbmt.2016.11.008" "Revista" => array:6 [ "tituloSerie" => "Biol Blood Marrow Transplant" "fecha" => "2017" "volumen" => "23" "paginaInicial" => "318" "paginaFinal" => "324" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27856368" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0485" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "γδ T-cell reconstitution after HLA-haploidentical hematopoietic transplantation depleted of TCR-αβ+/CD19+ lymphocytes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "I. Airoldi" 1 => "A. Bertaina" 2 => "I. Prigione" 3 => "A. Zorzoli" 4 => "D. Pagliara" 5 => "C. Cocco" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2014-09-599423" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2015" "volumen" => "125" "paginaInicial" => "2349" "paginaFinal" => "2358" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25612623" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0490" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatment of young patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia using increased dose of imatinib and deintensified chemotherapy before allogeneic stem cell transplantation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.M. Ribera" 1 => "O. García" 2 => "P. Montesinos" 3 => "S. Brunet" 4 => "E. Abella" 5 => "M. Barrios" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2141.2012.09240.x" "Revista" => array:6 [ "tituloSerie" => "Br J Haematol" "fecha" => "2012" "volumen" => "159" "paginaInicial" => "78" "paginaFinal" => "81" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22823211" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0495" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chemotherapy-phased imatinib pulses improve long-term outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: Northern Italy Leukemia Group protocol 09/00" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Bassan" 1 => "G. Rossi" 2 => "E.M. Pogliani" 3 => "E. di Bona" 4 => "E. Angelucci" 5 => "I. Cavattoni" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2010.28.1287" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2010" "volumen" => "28" "paginaInicial" => "3644" "paginaFinal" => "3652" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20606084" "web" => "Medline" ] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0500" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Achieving molecular remission before allogeneic stem cell transplantation in adult patients with philadelphia chromosome-positive acute lymphoblastic leukemia: impact on relapse and long-term outcome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. Lussana" 1 => "T. Intermesoli" 2 => "F. Gianni" 3 => "C. Boschini" 4 => "A. Masciulli" 5 => "O. Spinelli" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.bbmt.2016.07.021" "Revista" => array:6 [ "tituloSerie" => "Biol Blood Marrow Transplant" "fecha" => "2016" "volumen" => "22" "paginaInicial" => "1983" "paginaFinal" => "1987" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27492792" "web" => "Medline" ] ] ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0505" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Impact of MRD and TKI on allogeneic hematopoietic cell transplantation for Ph+ ALL: a study from the adult ALL WG of the JSHCT" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Nishiwaki" 1 => "K. Imai" 2 => "S. Mizuta" 3 => "H. Kanamori" 4 => "K. Ohashi" 5 => "T. Fukuda" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/bmt.2015.217" "Revista" => array:6 [ "tituloSerie" => "Bone Marrow Transplant" "fecha" => "2016" "volumen" => "51" "paginaInicial" => "43" "paginaFinal" => "50" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26389833" "web" => "Medline" ] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0510" "etiqueta" => "42" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long-term follow-up of the imatinib GRAAPH-2003 study in newly diagnosed patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: a GRAALL study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Tanguy-Schmidt" 1 => "P. Rousselot" 2 => "Y. Chalandon" 3 => "J.M. Cayuela" 4 => "S. Hayette" 5 => "M.C. Vekemans" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.bbmt.2012.08.021" "Revista" => array:6 [ "tituloSerie" => "Biol Blood Marrow Transplant" "fecha" => "2013" "volumen" => "19" "paginaInicial" => "150" "paginaFinal" => "155" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22960387" "web" => "Medline" ] ] ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0515" "etiqueta" => "43" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Complete hematologic and molecular response in adult patients with relapsed/refractory Philadelphia chromosome-positive B-precursor acute lymphoblastic leukemia following treatment with blinatumomab: results from a phase II, single-arm, multicenter study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. Martinelli" 1 => "N. Boissel" 2 => "P. Chevallier" 3 => "O. Ottmann" 4 => "N. Gökbuget" 5 => "M.S. Topp" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2016.69.3531" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2017" "volumen" => "35" "paginaInicial" => "1795" "paginaFinal" => "1802" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28355115" "web" => "Medline" ] ] ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0520" "etiqueta" => "44" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Longer follow-up confirms major improvement in outcome in children and adolescents with Philadelphia chromosome acute lymphoblastic leukaemia treated with continuous imatinib and haematopoietic stem cell transplantation. Results from the Spanish Cooperative Study SHOP/ALL-2005" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Rives" 1 => "M. Camós" 2 => "J. Estella" 3 => "P. Gómez" 4 => "M.J. Moreno" 5 => "J.L. Vivanco" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/bjh.12373" "Revista" => array:6 [ "tituloSerie" => "Br J Haematol" "fecha" => "2013" "volumen" => "162" "paginaInicial" => "419" "paginaFinal" => "421" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23668628" "web" => "Medline" ] ] ] ] ] ] ] ] 44 => array:3 [ "identificador" => "bib0525" "etiqueta" => "45" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Imatinib after induction for treatment of children and adolescents with Philadelphia-chromosome-positive acute lymphoblastic leukaemia (EsPhALL): a randomised, open-label, intergroup study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Biondi" 1 => "M. Schrappe" 2 => "P. de Lorenzo" 3 => "A. Castor" 4 => "G. Lucchini" 5 => "V. Gandemer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S1470-2045(12)70377-7" "Revista" => array:7 [ "tituloSerie" => "Lancet Oncol" "fecha" => "2012" "volumen" => "13" "paginaInicial" => "936" "paginaFinal" => "945" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22898679" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0140673616310121" "estado" => "S300" "issn" => "01406736" ] ] ] ] ] ] ] 45 => array:3 [ "identificador" => "bib0530" "etiqueta" => "46" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.H. Park" 1 => "I. Rivière" 2 => "M. Gonen" 3 => "X. Wang" 4 => "B. Sénéchal" 5 => "K.J. Curran" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1709919" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2018" "volumen" => "378" "paginaInicial" => "449" "paginaFinal" => "459" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29385376" "web" => "Medline" ] ] ] ] ] ] ] ] 46 => array:3 [ "identificador" => "bib0535" "etiqueta" => "47" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inotuzumab ozogamicin in combination with low-intensity chemotherapy for older patients with Philadelphia chromosome-negative acute lymphoblastic leukaemia: a single-arm, phase 2 study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H. Kantarjian" 1 => "F. Ravandi" 2 => "N.J. Short" 3 => "X. Huang" 4 => "N. Jain" 5 => "K. Sasaki" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S1470-2045(18)30011-1" "Revista" => array:6 [ "tituloSerie" => "Lancet Oncol" "fecha" => "2018" "volumen" => "19" "paginaInicial" => "240" "paginaFinal" => "248" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29352703" "web" => "Medline" ] ] ] ] ] ] ] ] 47 => array:3 [ "identificador" => "bib0540" "etiqueta" => "48" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Impact of minimal residual disease, detected by flow cytometry, on outcome of myeloablative hematopoietic cell transplantation for acute lymphoblastic leukemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Bar" 1 => "B.L. Wood" 2 => "J.P. Radich" 3 => "K.C. Doney" 4 => "A.E. Woolfrey" 5 => "C. Delaney" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1155/2014/421723" "Revista" => array:5 [ "tituloSerie" => "Leuk Res Treatment" "fecha" => "2014" "volumen" => "2014" "paginaInicial" => "421723" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24778882" "web" => "Medline" ] ] ] ] ] ] ] ] 48 => array:3 [ "identificador" => "bib0545" "etiqueta" => "49" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The effect of peritransplant minimal residual disease in adults with acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y. Zhou" 1 => "R. Slack" 2 => "J.L. Jorgensen" 3 => "S.A. Wang" 4 => "G. Rondon" 5 => "M. de Lima" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.clml.2014.01.002" "Revista" => array:6 [ "tituloSerie" => "Clin Lymphoma Myeloma Leuk" "fecha" => "2014" "volumen" => "14" "paginaInicial" => "319" "paginaFinal" => "326" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24548609" "web" => "Medline" ] ] ] ] ] ] ] ] 49 => array:3 [ "identificador" => "bib0550" "etiqueta" => "50" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Dhédin" 1 => "A. Huynh" 2 => "S. Maury" 3 => "R. Tabrizi" 4 => "K. Beldjord" 5 => "V. Asnafi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2014-09-599894" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2015" "volumen" => "125" "paginaInicial" => "2486" "paginaFinal" => "2496" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25587040" "web" => "Medline" ] ] ] ] ] ] ] ] 50 => array:3 [ "identificador" => "bib0555" "etiqueta" => "51" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Relationship between minimal residual disease measured by multiparametric flow cytometry prior to allogeneic hematopoietic stem cell transplantation and outcome in children with acute lymphoblastic leukemia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "I. Elorza" 1 => "C. Palacio" 2 => "J.L. Dapena" 3 => "L. Gallur" 4 => "J. Sánchez de Toledo" 5 => "C. Díaz de Heredia" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3324/haematol.2009.010843" "Revista" => array:7 [ "tituloSerie" => "Haematologica" "fecha" => "2010" "volumen" => "95" "paginaInicial" => "936" "paginaFinal" => "941" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20179088" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S2213858717304163" "estado" => "S300" "issn" => "22138587" ] ] ] ] ] ] ] 51 => array:3 [ "identificador" => "bib0560" "etiqueta" => "52" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Gökbuget" 1 => "H. Dombret" 2 => "M. Bonifacio" 3 => "A. Reichle" 4 => "C. Graux" 5 => "C. Faul" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Blood" "fecha" => "2018" "volumen" => "13" "paginaInicial" => "1522" "paginaFinal" => "1531" ] ] ] ] ] ] 52 => array:3 [ "identificador" => "bib0565" "etiqueta" => "53" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.L. Maude" 1 => "T.W. Laetsch" 2 => "J. Buechner" 3 => "S. Rives" 4 => "M. Boyer" 5 => "H. Bittencourt" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1709866" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2018" "volumen" => "378" "paginaInicial" => "439" "paginaFinal" => "448" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29385370" "web" => "Medline" ] ] ] ] ] ] ] ] 53 => array:3 [ "identificador" => "bib0570" "etiqueta" => "54" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Monitoring of minimal residual disease after allogeneic stem-cell transplantation in relapsed childhood acute lymphoblastic leukemia allows for the identification of impending relapse: results of the ALL-BFM-SCT 2003 trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Bader" 1 => "H. Kreyenberg" 2 => "A. von Stackelberg" 3 => "C. Eckert" 4 => "E. Salzmann-Manrique" 5 => "R. Meisel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2014.58.4631" "Revista" => array:7 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2015" "volumen" => "33" "paginaInicial" => "1275" "paginaFinal" => "1284" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25605857" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S1933287415003670" "estado" => "S300" "issn" => "19332874" ] ] ] ] ] ] ] 54 => array:3 [ "identificador" => "bib0575" "etiqueta" => "55" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Increasing mixed chimerism is an important prognostic factor for unfavorable outcome in children with acute lymphoblastic leukemia after allogeneic stem-cell transplantation: possible role for pre-emptive immunotherapy?" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Bader" 1 => "H. Kreyenberg" 2 => "W. Hoelle" 3 => "G. Dueckers" 4 => "R. Handgretinger" 5 => "P. Lang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2004.05.198" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2004" "volumen" => "22" "paginaInicial" => "1696" "paginaFinal" => "1705" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15117992" "web" => "Medline" ] ] ] ] ] ] ] ] 55 => array:3 [ "identificador" => "bib0580" "etiqueta" => "56" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Outcome of relapse after allogeneic HSCT in children with ALL enrolled in the ALL-SCT 2003/2007 trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Kuhlen" 1 => "A.M. Willasch" 2 => "J.H. Dalle" 3 => "J. Wachowiak" 4 => "I. Yaniv" 5 => "M. Ifversen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/bjh.14965" "Revista" => array:6 [ "tituloSerie" => "Br J Haematol" "fecha" => "2018" "volumen" => "180" "paginaInicial" => "82" "paginaFinal" => "89" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29193007" "web" => "Medline" ] ] ] ] ] ] ] ] 56 => array:3 [ "identificador" => "bib0585" "etiqueta" => "57" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Second hematopoietic stem cell transplantation for post-transplantation relapsed acute leukemia in children: a retrospective EBMT-PDWP study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "I. Yaniv" 1 => "A.C. Krauss" 2 => "E. Beohou" 3 => "A. Dalissier" 4 => "S. Corbacioglu" 5 => "M. Zecca" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.bbmt.2018.03.002" "Revista" => array:6 [ "tituloSerie" => "Biol Blood Marrow Transplant" "fecha" => "2018" "volumen" => "24" "paginaInicial" => "1629" "paginaFinal" => "131642" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29548831" "web" => "Medline" ] ] ] ] ] ] ] ] 57 => array:3 [ "identificador" => "bib0590" "etiqueta" => "58" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H. Kantarjian" 1 => "A. Stein" 2 => "N. Gökbuget" 3 => "A.K. Fielding" 4 => "A.C. Schuh" 5 => "J.M. Ribera" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1609783" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2017" "volumen" => "376" "paginaInicial" => "836" "paginaFinal" => "847" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28249141" "web" => "Medline" ] ] ] ] ] ] ] ] 58 => array:3 [ "identificador" => "bib0595" "etiqueta" => "59" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chimeric antigen receptor T cells for sustained remissions in leukemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.L. Maude" 1 => "N. Frey" 2 => "P.A. Shaw" 3 => "R. Aplenc" 4 => "D.M. Barrett" 5 => "N.J. Bunin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1407222" "Revista" => array:7 [ "tituloSerie" => "N Engl J Med" "fecha" => "2014" "volumen" => "371" "paginaInicial" => "1507" "paginaFinal" => "1517" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25317870" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0140673609600404" "estado" => "S300" "issn" => "01406736" ] ] ] ] ] ] ] 59 => array:3 [ "identificador" => "bib0600" "etiqueta" => "60" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inotuzumab ozogamicin, an anti-CD22-calecheamicin conjugate, for refractory and relapsed acute lymphocytic leukaemia: a phase 2 study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H. Kantarjian" 1 => "D. Thomas" 2 => "J. Jorgensen" 3 => "E. Jabbour" 4 => "P. Kebriaei" 5 => "M. Rytting" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S1470-2045(11)70386-2" "Revista" => array:6 [ "tituloSerie" => "Lancet Oncol" "fecha" => "2012" "volumen" => "13" "paginaInicial" => "403" "paginaFinal" => "411" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22357140" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015300000001/v1_201906260821/S238702061930275X/v1_201906260821/en/main.assets" "Apartado" => array:4 [ "identificador" => "44147" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Review" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015300000001/v1_201906260821/S238702061930275X/v1_201906260821/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S238702061930275X?idApp=UINPBA00004N"]

Statistics

Review

Allogeneic stem cell transplantation in the era of novel therapies for acute lymphoblastic leukaemia

El trasplante alogénico de progenitores hematopoyéticos en la era de las nuevas terapias en la leucemia linfoblástica aguda

Pere Barbaa,

Corresponding author

pbarba@vhio.net

Corresponding author.

, Izaskun Elorzab

a Servicio de Hematología, Hospital Universitario Vall d’Hebron-Universitat Autónoma de Barcelona, Barcelona, Spain

b Unidad de Trasplante de Progenitores Hematopoyéticos Pediátrica, Hospital Universitari Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain

Read

Times
was read the article

Total PDF

Total HTML

Share statistics

 array:24 [
  "pii" => "S238702061930275X"
  "issn" => "23870206"
  "doi" => "10.1016/j.medcle.2019.01.024"
  "estado" => "S300"
  "fechaPublicacion" => "2019-07-05"
  "aid" => "4763"
  "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46;. All rights reserved"
  "copyrightAnyo" => "2019"
  "documento" => "article"
  "crossmark" => 1
  "subdocumento" => "rev"
  "cita" => "Med Clin. 2019;153:28-34"
  "abierto" => array:3 [
    "ES" => false
    "ES2" => false
    "LATM" => false
  ]
  "gratuito" => false
  "lecturas" => array:1 [
    "total" => 0
  ]
  "Traduccion" => array:1 [
    "es" => array:19 [
      "pii" => "S0025775319300636"
      "issn" => "00257753"
      "doi" => "10.1016/j.medcli.2019.01.017"
      "estado" => "S300"
      "fechaPublicacion" => "2019-07-05"
      "aid" => "4763"
      "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46;"
      "documento" => "article"
      "crossmark" => 1
      "subdocumento" => "rev"
      "cita" => "Med Clin. 2019;153:28-34"
      "abierto" => array:3 [
        "ES" => false
        "ES2" => false
        "LATM" => false
      ]
      "gratuito" => false
      "lecturas" => array:2 [
        "total" => 18
        "formatos" => array:2 [
          "HTML" => 12
          "PDF" => 6
        ]
      ]
      "es" => array:12 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">Revisi&#243;n</span>"
        "titulo" => "El trasplante alog&#233;nico de progenitores hematopoy&#233;ticos en la era de las nuevas terapias en la leucemia linfobl&#225;stica aguda"
        "tienePdf" => "es"
        "tieneTextoCompleto" => "es"
        "tieneResumen" => array:2 [
          0 => "es"
          1 => "en"
        ]
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "28"
            "paginaFinal" => "34"
          ]
        ]
        "titulosAlternativos" => array:1 [
          "en" => array:1 [
            "titulo" => "Allogeneic stem cell transplantation&#160;in the era of novel therapies for acute lymphoblastic leukaemia"
          ]
        ]
        "contieneResumen" => array:2 [
          "es" => true
          "en" => true
        ]
        "contieneTextoCompleto" => array:1 [
          "es" => true
        ]
        "contienePdf" => array:1 [
          "es" => true
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "Pere Barba, Izaskun Elorza"
            "autores" => array:2 [
              0 => array:2 [
                "nombre" => "Pere"
                "apellidos" => "Barba"
              ]
              1 => array:2 [
                "nombre" => "Izaskun"
                "apellidos" => "Elorza"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "es"
      "Traduccion" => array:1 [
        "en" => array:9 [
          "pii" => "S238702061930275X"
          "doi" => "10.1016/j.medcle.2019.01.024"
          "estado" => "S300"
          "subdocumento" => ""
          "abierto" => array:3 [
            "ES" => false
            "ES2" => false
            "LATM" => false
          ]
          "gratuito" => false
          "lecturas" => array:1 [
            "total" => 0
          ]
          "idiomaDefecto" => "en"
          "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S238702061930275X?idApp=UINPBA00004N"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775319300636?idApp=UINPBA00004N"
      "url" => "/00257753/0000015300000001/v1_201906160629/S0025775319300636/v1_201906160629/es/main.assets"
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S2387020619302761"
    "issn" => "23870206"
    "doi" => "10.1016/j.medcle.2019.06.006"
    "estado" => "S300"
    "fechaPublicacion" => "2019-07-05"
    "aid" => "4775"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46;"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "sco"
    "cita" => "Med Clin. 2019;153:35-40"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:10 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Special article</span>"
      "titulo" => "Directed to consumer genetic testing&#46; Perspective from the Ethics commission of the Spanish Society for Human Genetics"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "35"
          "paginaFinal" => "40"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Pruebas gen&#233;ticas de venta directa a los consumidores&#46; Perspectiva de la Comisi&#243;n de &#201;tica de la Asociaci&#243;n Espa&#241;ola de Gen&#233;tica Humana"
        ]
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Teresa P&#224;mpols Ros, Jos&#233; Miguel Garc&#237;a Sagredo, Antonio P&#233;rez Ayt&#233;s, Aranzazu D&#237;az de Bustamante"
          "autores" => array:4 [
            0 => array:2 [
              "nombre" => "Teresa"
              "apellidos" => "P&#224;mpols Ros"
            ]
            1 => array:2 [
              "nombre" => "Jos&#233; Miguel"
              "apellidos" => "Garc&#237;a Sagredo"
            ]
            2 => array:2 [
              "nombre" => "Antonio"
              "apellidos" => "P&#233;rez Ayt&#233;s"
            ]
            3 => array:2 [
              "nombre" => "Aranzazu"
              "apellidos" => "D&#237;az de Bustamante"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S0025775319301228"
        "doi" => "10.1016/j.medcli.2019.01.028"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => false
          "ES2" => false
          "LATM" => false
        ]
        "gratuito" => false
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775319301228?idApp=UINPBA00004N"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020619302761?idApp=UINPBA00004N"
    "url" => "/23870206/0000015300000001/v1_201906260821/S2387020619302761/v1_201906260821/en/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S2387020619302748"
    "issn" => "23870206"
    "doi" => "10.1016/j.medcle.2018.11.022"
    "estado" => "S300"
    "fechaPublicacion" => "2019-07-05"
    "aid" => "4715"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46;"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "rev"
    "cita" => "Med Clin. 2019;153:16-27"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Review</span>"
      "titulo" => "Seasonal influenza in Spain&#58; Clinical and economic burden and vaccination programmes"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "16"
          "paginaFinal" => "27"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Gripe estacional en Espa&#241;a&#58; carga cl&#237;nica y econ&#243;mica y programas de vacunaci&#243;n"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:8 [
          "identificador" => "fig0010"
          "etiqueta" => "Fig&#46; 2"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "fuente" => "Adapted using data from the Spanish Influenza Surveillance System&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">23</span></a>"
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr2.jpeg"
              "Alto" => 1100
              "Ancho" => 2503
              "Tamanyo" => 95727
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Distribution of influenza cases by age group&#44; severe hospitalisations and deaths &#40;2011&#8211;2017&#41;&#46; SHCCI&#58; serious hospitalised confirmed cases of influenza&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Alberto P&#233;rez-Rubio, Leticia Platero, Jos&#233; Mar&#237;a Eiros Bouza"
          "autores" => array:3 [
            0 => array:2 [
              "nombre" => "Alberto"
              "apellidos" => "P&#233;rez-Rubio"
            ]
            1 => array:2 [
              "nombre" => "Leticia"
              "apellidos" => "Platero"
            ]
            2 => array:2 [
              "nombre" => "Jos&#233; Mar&#237;a"
              "apellidos" => "Eiros Bouza"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S0025775318307425"
        "doi" => "10.1016/j.medcli.2018.11.014"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => false
          "ES2" => false
          "LATM" => false
        ]
        "gratuito" => false
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775318307425?idApp=UINPBA00004N"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020619302748?idApp=UINPBA00004N"
    "url" => "/23870206/0000015300000001/v1_201906260821/S2387020619302748/v1_201906260821/en/main.assets"
  ]
  "en" => array:19 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Review</span>"
    "titulo" => "Allogeneic stem cell transplantation in the era of novel therapies for acute lymphoblastic leukaemia"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "28"
        "paginaFinal" => "34"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Pere Barba, Izaskun Elorza"
        "autores" => array:2 [
          0 => array:4 [
            "nombre" => "Pere"
            "apellidos" => "Barba"
            "email" => array:1 [
              0 => "pbarba@vhio.net"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "Izaskun"
            "apellidos" => "Elorza"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:2 [
          0 => array:3 [
            "entidad" => "Servicio de Hematolog&#237;a&#44; Hospital Universitario Vall d&#8217;Hebron-Universitat Aut&#243;noma de Barcelona&#44; Barcelona&#44; Spain"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Unidad de Trasplante de Progenitores Hematopoy&#233;ticos Pedi&#225;trica&#44; Hospital Universitari Sant Joan de D&#233;u&#44; Esplugues de Llobregat&#44; Barcelona&#44; Spain"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "El trasplante alog&#233;nico de progenitores hematopoy&#233;ticos en la era de las nuevas terapias en la leucemia linfobl&#225;stica aguda"
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Allogeneic haematopoietic stem cell transplantation &#40;allo-HSCT&#41; offers patients who suffer from acute lymphoblastic leukaemia &#40;ALL&#41; with high risk of relapse better survival compared to conventional chemotherapy&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">1</span></a> The optimisation of the transplant procedure and the greater facility to obtain compatible unrelated donors have meant that this therapy can today be offered to a greater number of patients&#44; achieve higher disease-free survival &#40;DFS&#41; results and obtain lower transplant-related mortality &#40;TRM&#41; rates&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The field of ALL has undergone a real revolution in recent years&#46; A greater biological knowledge of the disease has resulted in the appearance of numerous and innovative treatments&#44; many of them based on immunotherapy&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">3</span></a> These treatments include simple&#44; conjugated or bispecific monoclonal antibodies and chimeric antigen receptor T-cells &#40;CAR-T&#41; for CD19 positive B-precursor ALL&#46; While it seems evident that these new therapies will directly influence the treatment of ALL&#44; indications and implementation of allo-HSCT and current uncertainties regarding how exactly that will occur&#44; far exceeds what we do know for certain&#46; On this basis&#44; the purpose of this review is to summarise what we know about the role of haematopoietic stem cell transplantation &#40;HSCT&#41; in ALL and attempt to predict a possible direction on the positioning of this procedure in the near future&#44; in both adult and paediatric patients&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Transplantation indications</span><p id="par0015" class="elsevierStylePara elsevierViewall">The indications for transplantation in adults differ significantly from those of paediatric patients&#46; Because current indications for auto-HSCT in ALL are very residual&#44; we will only discuss indications for allo-HSCT&#44; except when explicitly mentioned&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows current indications for allo-HSCT according to the European Bone Marrow Transplant &#40;EBMT&#41; group&#44; while <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> contains indications from the PETHEMA group &#40;for adult patients&#41; and SHOP-PETHEMA 2013 &#40;for paediatric patients&#41;&#44; which are the cooperative groups in Spain&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Adult patients</span><p id="par0020" class="elsevierStylePara elsevierViewall">Despite achieving complete remissions in up to 90&#37; of patients&#44; relapses in adult patients are common&#44; affecting up to 50&#37; of patients who do not receive allo-HSCT&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">4</span></a> The prognosis of these relapsed patients is&#44; to date&#44; highly unfavourable&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">5</span></a> This is why allo-HSCT remains a fundamental pillar in the treatment of ALL&#44; either for first complete remission &#40;CR1&#41; or in patients with relapsed or refractory disease&#46; Currently&#44; ALL is the second most frequent indication for allo-HSCT in Europe and North America&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">6</span></a></p><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Allogeneic transplantation in first complete remission</span><p id="par0025" class="elsevierStylePara elsevierViewall">Several groups analysed the role of allo-HSCT in ALL in first remission &#40;CR1&#41;&#46; Most prospective comparative studies were developed in the late <span class="elsevierStyleSmallCaps">twentieth</span> century and were based on an genetic randomisation&#44; so that only patients with a histocompatible donor received allo-HSCT in CR1&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">1&#44;7</span></a> These studies showed that allo-HSCT was effective in reducing the risk of relapse&#44; with greater benefit in standard risk ALL&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">1</span></a> Evidence of the graft versus leukaemia effect in ALL has been reinforced in positive studies with infusion of donor lymphocytes and with the association of graft versus host disease &#40;GvHD&#41; development and a lower relapse rate&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">8</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The fact that a significant proportion of patients who did not receive an allo-HSCT in CR1 managed to achieve lasting remissions led several cooperative groups to improve the selection criteria of candidate patients&#46; These studies&#44; many based on treatment protocols inspired by paediatric regimens&#44; found that patients with a good clearance of measurable residual disease &#40;MRD&#41; could achieve durable remissions during treatment &#40;usually weeks 4&#8211;6 and weeks 16&#8211;18&#41; without an allo-HSCT in CR1&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">4</span></a> MRD can be determined through detection of leukaemic phenotype by flow cytometry and&#47;or determination of immunoglobulin receptors&#47;T cell by PCR techniques&#46; The sensitivity of PCR techniques is higher than that of cytometry&#44; although both have been shown to be feasible in clinical practice with high concordance between results&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">9</span></a> On this basis&#44; the current trend in most European cooperative groups is to reserve allo-HSCT in CR1 for at-risk patients&#44; mainly those with poor clearance of MRD and&#47;or with genetic criteria of poor prognosis at diagnosis&#44; such as t&#40;9&#59;22&#41; &#40;q34q11&#41;&#44; low hypodiploidy&#47;almost aneuploidy and complex karyotype&#46; At the molecular level&#44; deletions of IKZF-1&#44; rearrangements of KMT2A&#44; alterations of CRLF-2 and of the RAS pathway &#40;KRAS&#44; NRAS and PTPN1&#41;&#44; as well as Philadelphia-like subtype &#40;in which some of the mentioned alterations are included&#41; also suggest a bad prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">10</span></a> In T-ALL&#44; the absence of NOTCH-1 mutations and deletions of CDKN2A&#47;B are also considered to have poor prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">3</span></a> However&#44; there is no consensus on whether these changes should mean&#44; by themselves&#44; indication for transplantation in Ph negative B-ALL&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Classic clinical prognostic factors&#44; such as leukocytosis or CNS infiltration&#44; are not considered&#44; by themselves&#44; criteria to indicate allo-HSCT&#44; since genetics and MRD are attributed a greater risk of relapse and&#44; therefore&#44; indication of HSCT&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">11</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Allogeneic transplantation in second complete remission</span><p id="par0040" class="elsevierStylePara elsevierViewall">Currently available data show that the prognosis of patients with relapsed ALL is very unfavourable&#46; Although these patients are likely to achieve a second complete remission &#40;CR2&#41; &#40;30&#8211;50&#37;&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">5</span></a> successive relapses are very common&#44; which is why allo-HSCT is considered the only curative option for these patients after reaching a complete remission &#40;CR&#41;&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Paediatric patients</span><p id="par0045" class="elsevierStylePara elsevierViewall">Current chemotherapy protocols offer paediatric patients with ALL an 80&#37; chance of recovery&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">12</span></a> The group of patients with high-risk&#44; refractory or in early spinal relapse ALL &#40;10&#37; of all cases&#41; have a DFS of less than 40&#37; and are considered candidates for allo-HSCT&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">13</span></a> High-risk patients are considered those who do not achieve remission with induction treatment&#44; those who have detectable MRD after induction&#44; and in whom a positive MRD is detected during treatment&#46; MRD thresholds and the moment it is assessed vary according to the different study groups&#46;<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">12&#8211;14</span></a></p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Allogeneic transplantation in first complete remission</span><p id="par0050" class="elsevierStylePara elsevierViewall">The factors determining which patients are assigned to a more or less intense treatment group and indication of allo-HSCT in CR1 are clinical presentation&#44; genetics and response to treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">12</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">The indication for transplantation in CR1 is reserved for patients who have responded poorly to treatment or a persistence of MRD&#46; Study moments and MRD thresholds have been agreed on that predict a high risk of relapse and which are used for the indication of transplant&#46; Slow responders&#44; assessed at day seven and 14&#44; can be rescued with intensive treatment in 70&#37; of cases&#59; however&#44; those who do not achieve remission on day 28 have a 40&#37; DFS&#44; making them candidates for allo-HSCT in CR1&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">13</span></a> In late moments of treatment&#44; postconsolidation&#44; patients with positive MRD are considered suitable candidates for allo-HSCT in CR1&#46; Indication for allo-HSCT in CR1 is still being debated in patients with early T-cell precursor ALL&#44; infants under six months with MLL gene rearrangements and patients with hypodiploidy karyotype&#44; since it is disease with high resistance to chemotherapy&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">15</span></a> A summary of the results of allo-HSCT in paediatric patients in CR1 are&#58; an incidence of relapse rate of 10&#8211;20&#37;&#44; TRM 10&#8211;15&#37; and DFS 65&#8211;80&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">16</span></a></p><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Allogeneic transplantation in second complete remission</span><p id="par0060" class="elsevierStylePara elsevierViewall">Relapse occurs in 15&#8211;20&#37; of children who achieve remission after induction&#46; The duration of the first remission influences the likelihood of long-term survival&#44; such that early relapse &#40;within six months after treatment&#41; has less than a 40&#37; survival rate with chemotherapy alone&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">14</span></a> Extramedullary late and early relapses present good DFS results when chemotherapy is associated with local treatment&#46; Allo-HSCT in CR2 mainly benefits children with early medullary relapse and those who&#44; even when late&#44; show poor response to treatment&#46; The results of allo-HSCT in paediatric patients in CR2 are&#58; post-HSCT relapse incidence rate 20&#8211;40&#37;&#44; TRM 15&#8211;25&#37; and DFS 40&#8211;50&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">17</span></a> Children who receive transplants during successive remissions have very poor results even after receiving allo-HSCT&#44; with a DFS of approximately 30&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">14</span></a></p></span></span></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conditioning regimes</span><p id="par0065" class="elsevierStylePara elsevierViewall">Total body irradiation &#40;TBI&#41; at doses of 12<span class="elsevierStyleHsp" style=""></span>Gy combined with cyclophosphamide at a dose of 60<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day &#40;two days&#41; is considered the standard conditioning regimen for this patient group&#46; The TBI dose is fractionated into six sessions &#40;two sessions per day&#41;&#44; as a reduced toxicity is observed in the short- and long-term than when it is administered as a single dose&#46; The survival benefit of radiotherapy in paediatric patients has been demonstrated<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">18</span></a>&#59; however&#44; and despite its wide use&#44; evidence in adults is scarcer&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">19</span></a> Some groups have evaluated other strategies with radiation therapy at lower doses &#40;400<span class="elsevierStyleHsp" style=""></span>cGy&#41; or without radiation therapy&#44; and their results have been satisfactory and comparable to standard conditioning&#46;<a class="elsevierStyleCrossRefs" href="#bib0400"><span class="elsevierStyleSup">20&#44;21</span></a> In paediatric patients younger than three&#44; with a higher risk of secondary neoplasms and damage to neurological&#44; endocrine and growth development&#44; radiotherapy is replaced by intravenous busulfan&#44; at a dose according to the patient&#39;s weight and preferably by plasma levels&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">22</span></a> There is evidence that regimens without radiotherapy do not result in a worse control of the central nervous system disease compared to radiation therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">23</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">The introduction of reduced intensity &#40;RI&#41; regimens facilitated older patients and those with comorbidities&#8217; access to HSCT&#46; There are no randomised studies analysing the role of RI conditioning in ALL&#46; Retrospective studies have shown that this approach is viable in patients with ALL who are not candidates for allo-HSCT with conventional conditioning&#46;<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">24&#44;25</span></a> However&#44; some &#40;though not all&#41; retrospective comparative studies have questioned the benefit of RI allo-HSCT in elderly patients&#44; since the decrease in leukaemic relapse offered by allo-HSCT could not be compensated by the increase of the TRM&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">26</span></a> The benefit of RI allo-HSCT in paediatric patients is limited&#59; lower DFS than standard conditioning is offered&#44;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">27</span></a> but this is more an option for patients with accumulated morbidity and&#47;or in second transplants&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">The introduction in recent years of new drugs in the chemotherapy regimen prior to HSCT should be considered when evaluating possible post-HSCT toxicities&#46; Patients who have received rescue treatment with inotuzumab ozogamicin &#40;InO&#41; prior to transplantation have a higher risk of sinusoidal obstruction syndrome &#40;SOS&#41;&#46; In adults&#44; the incidence can reach 11&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">28</span></a> The risk is especially high in patients receiving two alkylating agents during conditioning&#44; such that avoiding this combination is prudent&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">29</span></a> The use of defibrotide as an SOS prophylaxis has proven useful in paediatric patients at high risk&#44;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">30</span></a> and is currently being investigated in adult patients&#46; The use of SOS prophylaxis in patients previously treated with InO could be considered while waiting for the results of ongoing clinical trials &#40;<a href="ctgov:NCT02851407">NCT02851407</a>&#41;&#44; although there is not yet any definitive evidence for it&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Donor sources and types</span><p id="par0080" class="elsevierStylePara elsevierViewall">All progenitor sources &#40;bone marrow &#91;BM&#93;&#44; peripheral blood &#91;PB&#93; and umbilical cord blood &#91;UCB&#93;&#41; commonly used for other indications&#44; as well as donor types&#44; have proven to be useful in ALL&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">The preferred source for paediatric patients is BM&#44; due to its lower incidence of chronic GvHD and long-term TRM compared to PB&#44;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">31</span></a> while in adults the most commonly used source is PB&#46; In the paediatric field&#44; UCB is a progenitor source for approximately 85&#8211;95&#37; of patients and has the advantages of rapid accessibility&#44; less restriction due to HLA compatibility&#44; greater ethnic variability and adequate cellularity for paediatric weight&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">32</span></a> Paediatric groups with UCB transplantation experience obtain results similar to BM<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">33</span></a> in ALL&#46; UCB has also been used with promising results in adult patients&#44;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">34</span></a> although its use is currently decreasing<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">35</span></a> and being substituted by haploidentical transplantation&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">There is less experience with haploidentical transplantations&#44; especially in a post-HSCT cyclophosphamide modality&#44; but the published data seem satisfactory&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">36</span></a> Experiences in haploidentical transplantation in paediatric patients is mainly based on ex vivo depletion platforms&#46; Currently the depletion of TCR lymphocytes &#945;&#946; allows infusion of haematopoietic progenitors&#44; NK cells and T lymphocytes &#947;&#948; with potent anti-infective and antileukaemic activity&#44; reaching immune reconstitution earlier&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">37</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">In summary&#44; in light of the published data&#44; the fact that indication for transplantation is for an ALL should not modify the choice of source or type of donor in a particular transplantation centre&#46; Moreover&#44; once the patient is in an optimal situation for the transplant&#44; one should proceed with the best donor available at that time without delaying the transplantation to search for an ideal donor&#44; since this delay could lead to relapse and in turn ineligibility for allo-HSCT&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Philadelphia positive B-acute lymphoblastic leukaemia</span><p id="par0100" class="elsevierStylePara elsevierViewall">Positive Philadelphia &#40;Ph&#43;&#41; B-ALL is&#44; also from an HSCT perspective&#44; a peculiar entity&#46; Because of its high risk of relapse in patients treated only with chemotherapy and tyrosine kinase inhibitors &#40;TKI&#41;&#44; the use of allo-HSCT in CR1 has been established&#46; The majority of studies into adults have shown long-term survival greater than 40&#37; in patients receiving allo-HSCT in CR1&#46;<a class="elsevierStyleCrossRefs" href="#bib0490"><span class="elsevierStyleSup">38&#44;39</span></a> The role of MRD positive prior to allo-HSCT is also important in B-ALL Ph&#43;&#44; and several studies have shown a worse prognosis in patients receiving allo-HSCT with positive MRD&#46;<a class="elsevierStyleCrossRefs" href="#bib0500"><span class="elsevierStyleSup">40&#44;41</span></a> In fact&#44; some protocols include an intensification or change of TKI to intensify response prior to transplantation and deepen the clearance of the MRD&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">38</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Using TKI in post-HSCT&#44; either as a universal treatment or as an anticipated treatment in the presence of detectable MRD&#44; is recommended&#46; However&#44; there is no consensus regarding which of these two approaches is best&#44; nor the choice of TKI or the duration of post-transplantation treatment&#46; Importantly&#44; TKIs have a non-negligible toxicity in post-HSCT&#44;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">42</span></a> especially in haematologic patients&#44; so its administration is not recommended for at least the first 30<span class="elsevierStyleHsp" style=""></span>days after transplantation&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Evidence has recently appeared that some patients with Ph&#43; B-ALL &#40;especially those with complete molecular remission&#41; can achieve durable responses with maintenance using new TKI&#44; preceded or not with auto-HSCT&#46; In this regard&#44; the French group demonstrated an OS of 80&#37; in patients who had received a auto-HSCT and maintenance treatment with imatinib&#44;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">42</span></a> and the Italian group recently showed<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">43</span></a> promising long-term survival with chemotherapy and maintenance with ponatinib in elderly patients who were not candidates for allo-HSCT&#46; It may be possible that new TKIs will mean that certain patients with Ph&#43; B-ALL will not have to undergo allo-HSCT in the future&#44; but such approaches should only be considered under research conditions for now&#46; Outside trail and research contexts&#44; allo-HSCT remains the standard for adult patients in CR1&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">38</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">In paediatric patients&#44; Ph positive ALL accounts for only 5&#37; of all ALL&#46; The addition of TKI to conventional chemotherapy has allowed similar results to be achieved in patients with Ph negative and positive ALL&#44;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">44</span></a> such that the indication for allo-HSCT in CR1 is reserved for patients with poor response to first-line treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">45</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">In patients with relapsed or refractory Ph positive ALL&#44; responses to new monoclonal antibodies such as blinatumomab or inotuzumab ozogamicin<a class="elsevierStyleCrossRefs" href="#bib0440"><span class="elsevierStyleSup">28&#44;43</span></a> and with CAR T-cells<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">46</span></a> have been described&#46; However&#44; these therapies have not yet modified indication for HSCT in patients with Ph positive ALL and its use is limited to patients with post-transplantation relapse or in a research context&#44; not candidates for transplantation&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">47</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Prognostic factors&#46; The role of measurable residual disease</span><p id="par0125" class="elsevierStylePara elsevierViewall">In patients with ALL who are candidates for allo-HSCT&#44; the presence of MRD during the chemotherapy treatment prior to transplantation seems to have an impact on prognosis&#46; Several groups<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">11&#44;48&#44;49</span></a> &#40;although not all&#41;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">50</span></a> have demonstrated the importance of this factor&#44; either through flow cytometry or PCR techniques&#46; Specifically&#44; the Italian group demonstrated that patients with MRD<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">&#8722;3</span> at week 16 and&#47;or 22 had worse results after allo-HSCT&#44; with a lower overall survival of 20&#37; and an relapse incidence rate within six years of 64&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">11</span></a> Others&#44; like the French group&#44; did not observe these differences when they analysed MRD in an earlier period &#40;week six&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">50</span></a> However&#44; in the French study this analysis was not included as a primary objective and performed only in a subset of patients &#40;only 54 patients received allo-HSCT with MRD<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">&#8722;3</span>&#41;&#44; so these results should be interpreted with caution&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">In children&#44; the impact of MRD prior to transplantation has been shown&#58; a DFS of 20&#37; was observed in patients with MRD<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">&#8722;4</span> and of 74&#37; in those with undetectable MRD by flow cytometry&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">51</span></a> In this study by the EUROCORD group&#44; the development of acute GvHD was associated with a lower risk of relapse&#44; especially in the positive MRD pre-HSCT group&#46; Given that the positive MRD pre-HSCT group had a lower DFS than those in the negative MRD group&#44; the need to use pre-HSCT immunotherapy treatment was considered&#44;<a class="elsevierStyleCrossRefs" href="#bib0560"><span class="elsevierStyleSup">52&#44;53</span></a> which could reduce MRD and thus achieve better post-HSCT results&#46; However&#44; there is currently no evidence of whether this strategy is more effective than performing a direct allo-HSCT with detectable MRD&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Regarding post-HSCT MRD&#44; its usefulness as a predictive factor of relapse has been demonstrated&#46; A study by the international BFM group showed that detection of MRD measured by flow cytometry after transplantation had an 87&#37; success rate of predicting leukaemic relapse within two months&#46;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">54</span></a> The determination of chimerism is complementary to the study of post-transplant MRD and the absence of a complete donor chimaera has been associated with an increased risk of relapse&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">55</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Relapse after allogeneic transplantation</span><p id="par0140" class="elsevierStylePara elsevierViewall">If paediatric patients who relapse after allo-HSCT go into remission and reach a second HSCT&#44; they have an DFS of 30&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">56</span></a> As mentioned&#44; the most important prognostic variable of DFS in a second HSCT is the duration of the first remission&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">14</span></a> Other better DFS factors include the absence of MRD and not having presented GvHD during the first HSCT&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Survival results after a second HSCT do not include the group of patients who do not reach a second HSCT&#46; Approximately 30&#37; of the patients who relapse pass away from refractory disease or due to the high toxicity associated with the aggressiveness of the rescue treatments&#44; given that they are often patients with frequent morbidities and accumulated toxicity&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Recent studies suggest that certain paediatric patients with early relapse post-HSCT&#44; comorbidities or persistence of MRD would be candidates for immunotherapy before a second HSCT or even as replacement therapy for HSCT&#46;<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">57</span></a> Clinical trials have shown that therapy with CAR-T anti-CD19 is very effective in children with CD19&#43; ALL who have relapsed after allo-HSCT&#44; achieving complete remissions with a seemingly lower toxicity than conventional treatments&#44; especially in patients with low tumour load&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">53</span></a> Treatment with blinatumomab or InO for patients with post-HSCT relapse may be another alternative therapy to traditional chemotherapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0440"><span class="elsevierStyleSup">28&#44;58</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Future perspectives in the era of new treatments</span><p id="par0155" class="elsevierStylePara elsevierViewall">Immunotherapy is changing the way we treat ALL&#46; Whether these advances will lead to changes in indications or even in conditioning treatments for these patients is still to be seen&#46; Some recent studies have suggested<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">46</span></a> that certain therapies&#44; especially CAR-T&#44; might replace HSCT and lead to a decrease in transplantations to treat this disease&#46; In this sense&#44; long-lasting remissions have been observed in patients with relapsed ALL after administering CAR T-cells&#44; even without a subsequent allo-HSCT&#46;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">59</span></a> Conversely&#44; these new tools may improve the treatment of patients who are refractory or relapsing and allow allo-HSCT to treat patients who are unable to be treated with HSCT&#46; In addition&#44; CAR-T can clarify the presence of MRD with a much lower toxicity than conventional chemotherapy and treat the patient with allo-HSCT and with lower morbidities and&#44; therefore&#44; lower toxicity&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">The new monoclonal antibodies&#44; such as blinatumomab or InO&#44; among others&#44; have shown the ability to induce complete quality responses&#44; with very low or even undetectable MRD&#44; in a percentage of patients significantly higher than conventional chemotherapy&#44;<a class="elsevierStyleCrossRefs" href="#bib0590"><span class="elsevierStyleSup">58&#44;60</span></a> although these responses are usually short-lived and a subsequent allo-HSCT is required&#46; Whether these and other monoclonal antibodies in first-line treatment can reduce relapses to initial treatment and thus decrease the number of patient candidates for transplantation is yet to be confirmed&#46; Finally&#44; it is important to note that most treatments based on immunotherapy today are only effective against B-lineage ALL&#46; This is why there are not as many prospects for changes in HSCT indication for T-ALL&#44; at least in the short term&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conclusions</span><p id="par0165" class="elsevierStylePara elsevierViewall">Despite all the advances in the management of patients with ALL&#44; allo-HSCT remains a fundamental pillar of treatment&#46; HSCT achieves lasting responses in patients with clinical and biological characteristics of poor prognosis and in patients with relapse or refractory disease&#46; The continuous optimisation of the procedure&#44; improvements in the selection of transplantation candidates&#44; the greater availability of donors at the optimal time &#40;thanks&#44; mainly&#44; to haploidentical transplants&#41; and the use of therapies to prevent relapse of the underlying disease&#44; should all facilitate further improvement of the prognosis of these patients beyond what we have already seen in the last decades in paediatric patients and&#44; to a lesser extent&#44; in adult patients&#46; Patients with positive MRD prior to transplantation may be candidates for immunotherapy with CAR-T or monoclonal antibodies with the objective of improving DFS&#46; Another group that can benefit from these therapies is those patients who relapse after an allo-HSCT&#44; especially those that present early relapse and&#47;or associate morbidities and&#47;or refractory disease&#46; The intention of immunotherapy in these cases is to control the disease with as little toxicity as possible&#44; and in some cases to achieve prolonged remissions&#44; when faced with the impossibility of performing a second HSCT&#46; And the possibility that these therapies in themselves may be curative for certain patients is currently under study&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Funding</span><p id="par0170" class="elsevierStylePara elsevierViewall">PB received funding from the <span class="elsevierStyleGrantSponsor" id="gs1">Carlos III Institute of Health</span> FIS16&#47;01433 project and a PERIS 2018&#8211;2020 grant from the <span class="elsevierStyleGrantSponsor" id="gs2">Generalitat de Catalunya</span> &#40;<span class="elsevierStyleGrantNumber" refid="gs2">BDNS357800</span>&#41;&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflict of interest</span><p id="par0175" class="elsevierStylePara elsevierViewall">PB has received funding for advice and&#47;or travel from Amgen&#44; Pfizer&#44; Novartis&#44; Jazz Pharmaceuticals and Shire&#44; without affecting the content of this review&#46; IE declares no conflict of interest&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:16 [
        0 => array:3 [
          "identificador" => "xres1211919"
          "titulo" => "Abstract"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0005"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1127989"
          "titulo" => "Keywords"
        ]
        2 => array:3 [
          "identificador" => "xres1211918"
          "titulo" => "Resumen"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0010"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec1127990"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Transplantation indications"
          "secciones" => array:2 [
            0 => array:3 [
              "identificador" => "sec0015"
              "titulo" => "Adult patients"
              "secciones" => array:2 [
                0 => array:2 [
                  "identificador" => "sec0020"
                  "titulo" => "Allogeneic transplantation in first complete remission"
                ]
                1 => array:2 [
                  "identificador" => "sec0025"
                  "titulo" => "Allogeneic transplantation in second complete remission"
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "sec0030"
              "titulo" => "Paediatric patients"
              "secciones" => array:1 [
                0 => array:3 [
                  "identificador" => "sec0035"
                  "titulo" => "Allogeneic transplantation in first complete remission"
                  "secciones" => array:1 [
                    0 => array:2 [
                      "identificador" => "sec0040"
                      "titulo" => "Allogeneic transplantation in second complete remission"
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
        6 => array:2 [
          "identificador" => "sec0045"
          "titulo" => "Conditioning regimes"
        ]
        7 => array:2 [
          "identificador" => "sec0050"
          "titulo" => "Donor sources and types"
        ]
        8 => array:2 [
          "identificador" => "sec0055"
          "titulo" => "Philadelphia positive B-acute lymphoblastic leukaemia"
        ]
        9 => array:2 [
          "identificador" => "sec0060"
          "titulo" => "Prognostic factors&#46; The role of measurable residual disease"
        ]
        10 => array:2 [
          "identificador" => "sec0065"
          "titulo" => "Relapse after allogeneic transplantation"
        ]
        11 => array:2 [
          "identificador" => "sec0070"
          "titulo" => "Future perspectives in the era of new treatments"
        ]
        12 => array:2 [
          "identificador" => "sec0075"
          "titulo" => "Conclusions"
        ]
        13 => array:2 [
          "identificador" => "sec0080"
          "titulo" => "Funding"
        ]
        14 => array:2 [
          "identificador" => "sec0085"
          "titulo" => "Conflict of interest"
        ]
        15 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2018-07-31"
    "fechaAceptado" => "2019-01-09"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1127989"
          "palabras" => array:5 [
            0 => "Allogeneic transplantation"
            1 => "Acute lymphoblastic leukaemia"
            2 => "Immunotherapy"
            3 => "Monoclonal antibodies"
            4 => "CAR-T"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1127990"
          "palabras" => array:5 [
            0 => "Trasplante alog&#233;nico"
            1 => "Leucemia linfobl&#225;stica aguda"
            2 => "Inmunoterapia"
            3 => "Anticuerpos monoclonales"
            4 => "CAR-T"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Immunotherapy is changing the treatment of acute lymphoblastic leukaemia &#40;ALL&#41; in adults and children&#46; However&#44; regardless of these new therapies&#44; allogeneic hematopoietic cell transplantation &#40;allo-HCT&#41; still play a key role in the treatment of ALL&#44; although it is uncertain how these new therapies will impact on the transplant procedure and indications&#46; This article reviews the indications of allo-HCT for children and adults diagnosed with ALL&#44; the different sources and conditioning regimens for transplantation as well as the role of measurable residual diseases pre- and post-HCT in the era of the new therapies for ALL&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La inmunoterapia est&#225; cambiando profundamente el tratamiento de la leucemia linfobl&#225;stica aguda &#40;LLA&#41; infantil y del adulto&#46; Sin embargo&#44; a pesar de todos los avances&#44; el trasplante alog&#233;nico de progenitores hematopoy&#233;ticos &#40;alo-TPH&#41; sigue siendo un pilar fundamental en su tratamiento&#46; C&#243;mo van a modificar estas nuevas terapias la indicaci&#243;n y el procedimiento de trasplante&#44; resulta todav&#237;a incierto&#46; En el presente art&#237;culo se discuten las indicaciones de TPH en la LLA infantil y del adulto&#44; las posibles fuentes de donantes y acondicionamiento&#44; as&#237; como el papel de la enfermedad residual medible en el contexto de la nueva era de tratamientos en el campo de la LLA&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0040">Please cite this article as&#58; Barba P&#44; Elorza I&#46; El trasplante alog&#233;nico de progenitores hematopoy&#233;ticos en la era de las nuevas terapias en la leucemia linfobl&#225;stica aguda&#46; Med Clin &#40;Barc&#41;&#46; 2019&#59;153&#58;28&#8211;34&#46;</p>"
      ]
    ]
    "multimedia" => array:2 [
      0 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Indication&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HLA 10&#47;10<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Alternative donor<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Observations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Adult patients</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ph negative ALL in CR1&#44; good clearance of MRD and no genetic factors of poor prognosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not recommended&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not recommended&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ph negative ALL in CR1&#44; good clearance of MRD and with genetic factors of poor prognosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Clinical option&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Clinical option&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">In the case of alternative donors&#44; consider the risk of theoretical TRM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ph negative ALL in CR1&#44; slow clearance of MRD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Standard&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Standard&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Try to perform HSCT in negative MRD or at least as low as possible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ph negative ALL in incipient relapse&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Standard&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Standard&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">As far as possible&#44; perform some non-toxic treatment to proceed to HSCT in MRD negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ph negative ALL in CR2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Standard&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Standard&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ph negative ALL in refractoriness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not recommended&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not recommended&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ph positive ALL in CR1 without detectable MRD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Standard&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Standard&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">In patients without donor or at high risk of TRM&#44; ABSCT and subsequent maintenance with TKI can be considered&#46; Ideally in a clinical trial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ph positive ALL in CR1 with detectable MRD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Clinical option&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Clinical option&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">If possible&#44; change TKI to deepen the response prior to HSCT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ph positive ALL in CR2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Clinical option&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Clinical option&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Standard&#44; if for some reason HSCT was not performed in CR1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ph positive or negative ALL in refractoriness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not recommended&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not recommended&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Paediatric patients</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Low-risk ALL<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a> in CR1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not recommended&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not recommended&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Good results with chemotherapy&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>High risk<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a> ALL in CR1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Standard&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Clinical option&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Use of all sources and donors&#46; Use the one that is available at the optimum time for the transplant according to the centre&#39;s protocol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>ALL in CR2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Standard&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Clinical option&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Try to perform HSCT in negative MRD or at least as low as possible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>ALL in CR &#62;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Standard&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Clinical option&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">As far as possible&#44; perform some non-toxic treatment to proceed to HSCT in MRD negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2068976.png"
              ]
            ]
          ]
          "notaPie" => array:3 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Family or unrelated donor&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Alternative donor&#58; HLA 9&#47;10&#44; haploidentical or umbilical cord blood&#46;</p>"
            ]
            2 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "c"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Categories based on the number of leukocytes at diagnosis&#44; cytogenetics&#44; molecular markers and time to remission&#46;</p> <p class="elsevierStyleNotepara" id="npar0020">MRD&#58; measurable residual disease&#59; HLA&#58; human leucocyte antigen&#59; TKI&#58; tyrosine kinase inhibitors&#59; ALL&#58; acute lymphoblastic leukaemia&#59; TRM&#58; transplant related mortality&#59; Ph&#58; Philadelphia&#59; CR&#58; complete response&#59; ABSCT&#58; autologous peripheral blood stem cell transplant&#59; HSCT&#58; hematopoietic stem cell transplantation&#46;</p> <p class="elsevierStyleNotepara" id="npar0025">Authors&#8217; recommendations based on EBMT transplantation indications &#40;Sureda et al&#46; Bone Marrow Transplantation&#59; 2015&#41;&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Indications of allogeneic transplantation in adult acute lymphoblastic leukaemia depending on the clinical situation according to the <span class="elsevierStyleItalic">European Society for Bone and Marrow Transplantation</span> &#40;EBMT&#41;&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "tablatextoimagen" => array:2 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Adult patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">First referral</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>No cytological complete remission after induction &#40;day &#43;28&#41; or complete remission with MRD<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>10&#8722;3 measured by flow cytometry&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>MRD<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>10&#8722;4 measured by flow cytometry after block B3 consolidation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Emergence of positive MRD at some point in the follow-up beyond block B3 consolidation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Second referral</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>All patients who are transplant candidates<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2068975.png"
              ]
            ]
            1 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Paediatric patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">First referral</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>No cytomorphologic complete remission after induction A &#40;day &#43;33&#41;&#44; confirmed by flow cytometry&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>MRD<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">&#8722;2</span> after induction A &#40;day &#43;33&#41; and MRD<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">&#8722;3</span> at day &#43;78 &#40;prior to consolidation or at block HR-1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>At t&#40;4&#59;11&#41; with MRD<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">&#8722;3</span> at day &#43;78 &#40;prior to block HR-1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>In hypodiploidy &#40;&#60;<span class="elsevierStyleHsp" style=""></span>44 chromosomes&#41; with MRD<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>10&#8722;3 at day &#43;78 &#40;prior to block HR-1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>In T-ALL with poor response to prednisone and MRD<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>10&#8722;3 at day &#43;78 &#40;prior to block HR-1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>In HR patients if MRD is persistently positive<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>10&#8722;4 &#40;after third block HR-3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Second referral</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Relapse of ALL phenotype T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Early medullary relapse of precursor-B ALL &#40;&#60;36<span class="elsevierStyleHsp" style=""></span>months from diagnosis&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Early extramedullary relapse of precursor-B ALL &#40;&#60;18<span class="elsevierStyleHsp" style=""></span>months from diagnosis&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Late relapse of precursor-B ALL with poor response to chemotherapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2068974.png"
              ]
            ]
          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0020"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0030">This is a recommendation&#46; The protocol does not specifically include patients in CR2&#46;</p> <p class="elsevierStyleNotepara" id="npar0035">HR&#58; high risk&#59; MRD&#58; measurable residual disease&#59; ALL&#58; acute lymphoblastic leukaemia&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Indications for allogeneic transplantation in acute lymphoblastic leukaemia in high-risk adult &#40;PETHEMA AR-2011 Protocol&#41; and paediatric patients &#40;LAL&#47;SHOP-Pethema 2013 Protocol&#41;&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:60 [
            0 => array:3 [
              "identificador" => "bib0305"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "In adults with standard-risk acute lymphoblastic leukemia&#44; the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission&#44; and an autologous transplantation is less effective than conventional consolidation&#47;maintenance chemotherapy in all patients&#58; final results of the International ALL Trial &#40;MRC UKALL XII&#47;ECOG E2993&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;H&#46; Goldstone"
                            1 => "S&#46;M&#46; Richards"
                            2 => "H&#46;M&#46; Lazarus"
                            3 => "M&#46;S&#46; Tallman"
                            4 => "G&#46; Buck"
                            5 => "A&#46;K&#46; Fielding"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1182/blood-2007-10-116582"
                      "Revista" => array:6 [
                        "tituloSerie" => "Blood"
                        "fecha" => "2008"
                        "volumen" => "111"
                        "paginaInicial" => "1827"
                        "paginaFinal" => "1833"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18048644"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0310"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Reduced mortality after allogeneic hematopoietic-cell transplantation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46;A&#46; Gooley"
                            1 => "J&#46;W&#46; Chien"
                            2 => "S&#46;A&#46; Pergam"
                            3 => "S&#46; Hingorani"
                            4 => "M&#46;L&#46; Sorror"
                            5 => "M&#46; Boeckh"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1004383"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2010"
                        "volumen" => "363"
                        "paginaInicial" => "2091"
                        "paginaFinal" => "2101"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21105791"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0315"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Acute lymphoblastic leukemia in adults&#58; steps ahead"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;M&#46; Ribera"
                            1 => "S&#46; Vives"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Med Clin &#40;Barc&#41;"
                        "fecha" => "2017"
                        "volumen" => "149"
                        "paginaInicial" => "119"
                        "paginaFinal" => "121"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0320"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treatment of high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in adolescents and adults according to early cytologic response and minimal residual disease after consolidation assessed by flow cytometry&#58; final results of the PETHEMA ALL-AR-03 trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;M&#46; Ribera"
                            1 => "A&#46; Oriol"
                            2 => "M&#46; Morgades"
                            3 => "P&#46; Montesinos"
                            4 => "J&#46; Sarr&#224;"
                            5 => "J&#46; Gonz&#225;lez-Campos"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2013.52.2425"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2014"
                        "volumen" => "32"
                        "paginaInicial" => "1595"
                        "paginaFinal" => "1604"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24752047"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0325"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA Study Group"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Oriol"
                            1 => "S&#46; Vives"
                            2 => "J&#46;M&#46; Hern&#225;ndez-Rivas"
                            3 => "M&#46; Tormo"
                            4 => "I&#46; Heras"
                            5 => "C&#46; Rivas"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3324/haematol.2009.014274"
                      "Revista" => array:6 [
                        "tituloSerie" => "Haematologica"
                        "fecha" => "2010"
                        "volumen" => "95"
                        "paginaInicial" => "589"
                        "paginaFinal" => "596"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20145276"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0330"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Use of haploidentical stem cell transplantation continues to increase&#58; the 2015 European Society for Blood and Marrow Transplant activity survey report"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;R&#46; Passweg"
                            1 => "H&#46; Baldomero"
                            2 => "P&#46; Bader"
                            3 => "C&#46; Bonini"
                            4 => "R&#46;F&#46; Duarte"
                            5 => "C&#46; Dufour"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/bmt.2017.34"
                      "Revista" => array:6 [
                        "tituloSerie" => "Bone Marrow Transplant"
                        "fecha" => "2017"
                        "volumen" => "52"
                        "paginaInicial" => "811"
                        "paginaFinal" => "817"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28287639"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0335"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Myeloablative allogeneic versus autologous stem cell transplantation in adult patients with acute lymphoblastic leukemia in first remission&#58; a prospective sibling donor versus no-donor comparison"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;J&#46; Cornelissen"
                            1 => "B&#46; van der Holt"
                            2 => "G&#46;E&#46; Verhoef"
                            3 => "M&#46;B&#46; van&#8217;t Veer"
                            4 => "M&#46;H&#46; van Oers"
                            5 => "H&#46;C&#46; Schouten"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1182/blood-2008-07-168625"
                      "Revista" => array:7 [
                        "tituloSerie" => "Blood"
                        "fecha" => "2009"
                        "volumen" => "113"
                        "paginaInicial" => "1375"
                        "paginaFinal" => "1382"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18988865"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0939475314001732"
                          "estado" => "S300"
                          "issn" => "09394753"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0340"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "NIH-defined graft-versus-host disease and evidence for a potent graft-versus-leukemia effect in patients with acute lymphoblastic leukemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46;H&#46; Terwey"
                            1 => "T&#46;M&#46; le Duc"
                            2 => "P&#46;G&#46; Hemmati"
                            3 => "P&#46; le Coutre"
                            4 => "M&#46; Nagy"
                            5 => "P&#46; Martus"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/annonc/mds615"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Oncol"
                        "fecha" => "2013"
                        "volumen" => "24"
                        "paginaInicial" => "1363"
                        "paginaFinal" => "1370"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23247660"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0345"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Flow cytometry and IG&#47;TCR quantitative PCR for minimal residual disease quantitation in acute lymphoblastic leukemia&#58; a French multicenter prospective study on behalf of the FRALLE&#44; EORTC and GRAALL"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46; Garand"
                            1 => "K&#46; Beldjord"
                            2 => "H&#46; Cav&#233;"
                            3 => "C&#46; Fossat"
                            4 => "I&#46; Arnoux"
                            5 => "V&#46; Asnafi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/leu.2012.234"
                      "Revista" => array:6 [
                        "tituloSerie" => "Leukemia"
                        "fecha" => "2013"
                        "volumen" => "27"
                        "paginaInicial" => "370"
                        "paginaFinal" => "376"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23070018"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0350"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Genetics and prognosis of ALL in children vs adults"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "K&#46;G&#46; Roberts"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1182/asheducation-2018.1.137"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hematology Am Soc Hematol Educ Program"
                        "fecha" => "2018"
                        "volumen" => "2018"
                        "paginaInicial" => "137"
                        "paginaFinal" => "145"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30504302"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0355"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Different molecular levels of post-induction minimal residual disease may predict hematopoietic stem cell transplantation outcome in adult Philadelphia-negative acute lymphoblastic leukemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46; Bassan"
                            1 => "O&#46; Spinelli"
                            2 => "E&#46; Oldani"
                            3 => "T&#46; Intermesoli"
                            4 => "M&#46; Tosi"
                            5 => "B&#46; Peruta"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/bcj.2014.48"
                      "Revista" => array:5 [
                        "tituloSerie" => "Blood Cancer J"
                        "fecha" => "2014"
                        "volumen" => "4"
                        "paginaInicial" => "e225"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25014772"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0360"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk- and response-based classification of childhood B-precursor acute lymphoblastic leukemia&#58; a combined analysis of prognostic markers from the Pediatric Oncology Group &#40;POG&#41; and Children&#39;s Cancer Group &#40;CCG&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46;R&#46; Schultz"
                            1 => "D&#46;J&#46; Pullen"
                            2 => "H&#46;N&#46; Sather"
                            3 => "J&#46;J&#46; Shuster"
                            4 => "M&#46; Devidas"
                            5 => "M&#46;J&#46; Borowitz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1182/blood-2006-01-024729"
                      "Revista" => array:7 [
                        "tituloSerie" => "Blood"
                        "fecha" => "2007"
                        "volumen" => "109"
                        "paginaInicial" => "926"
                        "paginaFinal" => "935"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17003380"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S014067361631460X"
                          "estado" => "S300"
                          "issn" => "01406736"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0365"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Outcomes after induction failure in childhood acute lymphoblastic leukemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Schrappe"
                            1 => "S&#46;P&#46; Hunger"
                            2 => "C&#46;H&#46; Pui"
                            3 => "V&#46; Saha"
                            4 => "P&#46;S&#46; Gaynon"
                            5 => "A&#46; Baruchel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1110169"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2012"
                        "volumen" => "366"
                        "paginaInicial" => "1371"
                        "paginaFinal" => "1381"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22494120"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0370"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Outcome of children with multiply relapsed B-cell acute lymphoblastic leukemia&#58; a therapeutic advances in childhood leukemia &#38; lymphoma study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "W&#46; Sun"
                            1 => "J&#46; Malvar"
                            2 => "R&#46; Sposto"
                            3 => "A&#46; Verma"
                            4 => "J&#46;J&#46; Wilkes"
                            5 => "R&#46; Dennis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/s41375-018-0094-0"
                      "Revista" => array:2 [
                        "tituloSerie" => "Leukemia"
                        "fecha" => "2018"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0375"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Improved outcome with hematopoietic stem cell transplantation in a poor prognostic subgroup of infants with mixed-lineage-leukemia &#40;MLL&#41;-rearranged acute lymphoblastic leukemia&#58; results from the Interfant-99 Study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46; Mann"
                            1 => "A&#46; Attarbaschi"
                            2 => "M&#46; Schrappe"
                            3 => "P&#46; de Lorenzo"
                            4 => "C&#46; Peters"
                            5 => "I&#46; Hann"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1182/blood-2010-03-273532"
                      "Revista" => array:6 [
                        "tituloSerie" => "Blood"
                        "fecha" => "2010"
                        "volumen" => "116"
                        "paginaInicial" => "2644"
                        "paginaFinal" => "2650"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20592248"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0380"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Stem-cell transplantation in children with acute lymphoblastic leukemia&#58; a prospective international multicenter trial comparing sibling donors with matched unrelated donors&#8212;the ALL-SCT-BFM-2003 trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Peters"
                            1 => "M&#46; Schrappe"
                            2 => "A&#46; von Stackelberg"
                            3 => "A&#46; Schrauder"
                            4 => "P&#46; Bader"
                            5 => "W&#46; Ebell"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2014.58.9747"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2015"
                        "volumen" => "33"
                        "paginaInicial" => "1265"
                        "paginaFinal" => "1274"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25753432"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0385"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Outcomes after HLA-matched sibling transplantation or chemotherapy in children with B-precursor acute lymphoblastic leukemia in a second remission&#58; a collaborative study of the Children&#39;s Oncology Group and the Center for International Blood and Marrow Transplant Research"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Eapen"
                            1 => "E&#46; Raetz"
                            2 => "M&#46;J&#46; Zhang"
                            3 => "C&#46; Muehlenbein"
                            4 => "M&#46; Devidas"
                            5 => "T&#46; Abshire"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1182/blood-2005-12-4942"
                      "Revista" => array:6 [
                        "tituloSerie" => "Blood"
                        "fecha" => "2006"
                        "volumen" => "107"
                        "paginaInicial" => "4961"
                        "paginaFinal" => "4967"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16493003"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0390"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Factors associated with long-term risk of relapse after unrelated cord blood transplantation in children with acute lymphoblastic leukemia in remission"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46;M&#46; Page"
                            1 => "M&#46; Labopin"
                            2 => "A&#46; Ruggeri"
                            3 => "G&#46; Michel"
                            4 => "C&#46; Diaz de Heredia"
                            5 => "T&#46; O&#8217;Brien"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.bbmt.2017.04.015"
                      "Revista" => array:6 [
                        "tituloSerie" => "Biol Blood Marrow Transplant"
                        "fecha" => "2017"
                        "volumen" => "23"
                        "paginaInicial" => "1350"
                        "paginaFinal" => "1358"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28438676"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0395"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A comparison of cyclophosphamide and total body irradiation with etoposide and total body irradiation as conditioning regimens for patients undergoing sibling allografting for acute lymphoblastic leukemia in first or second complete remission"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46;I&#46; Marks"
                            1 => "S&#46;J&#46; Forman"
                            2 => "K&#46;G&#46; Blume"
                            3 => "W&#46;S&#46; P&#233;rez"
                            4 => "D&#46;J&#46; Weisdorf"
                            5 => "A&#46; Keating"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.bbmt.2005.12.029"
                      "Revista" => array:6 [
                        "tituloSerie" => "Biol Blood Marrow Transplant"
                        "fecha" => "2006"
                        "volumen" => "12"
                        "paginaInicial" => "438"
                        "paginaFinal" => "453"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16545728"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0400"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Allogeneic stem cell transplantation after conditioning with treosulfan&#44; etoposide and cyclophosphamide for patients with ALL&#58; a phase II-study on behalf of the German Cooperative Transplant Study Group and ALL Study Group &#40;GMALL&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Kr&#246;ger"
                            1 => "M&#46; Bornh&#228;user"
                            2 => "M&#46; Stelljes"
                            3 => "U&#46; Pichlmeier"
                            4 => "R&#46; Trenschel"
                            5 => "C&#46; Schmid"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/bmt.2015.202"
                      "Revista" => array:6 [
                        "tituloSerie" => "Bone Marrow Transplant"
                        "fecha" => "2015"
                        "volumen" => "50"
                        "paginaInicial" => "1503"
                        "paginaFinal" => "1507"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26367236"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0405"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Intravenous busulfan compared with total body irradiation pretransplant conditioning for adults with acute lymphoblastic leukemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46; Kebriaei"
                            1 => "C&#46; Anasetti"
                            2 => "M&#46;J&#46; Zhang"
                            3 => "H&#46;L&#46; Wang"
                            4 => "I&#46; Aldoss"
                            5 => "M&#46; de Lima"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.bbmt.2017.11.025"
                      "Revista" => array:6 [
                        "tituloSerie" => "Biol Blood Marrow Transplant"
                        "fecha" => "2018"
                        "volumen" => "24"
                        "paginaInicial" => "726"
                        "paginaFinal" => "733"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29197676"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0410"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk factors for subsequent central nervous system tumors in pediatric allogeneic hematopoietic cell transplant&#58; a study from the center for international blood and marrow transplant research &#40;CIBMTR&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Gabriel"
                            1 => "B&#46;E&#46; Shaw"
                            2 => "R&#46; Brazauskas"
                            3 => "M&#46; Chen"
                            4 => "D&#46;A&#46; Margolis"
                            5 => "H&#46; Sengelov"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.bbmt.2017.04.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Biol Blood Marrow Transplant"
                        "fecha" => "2017"
                        "volumen" => "23"
                        "paginaInicial" => "1320"
                        "paginaFinal" => "1326"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28411175"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0415"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Outcome analysis of pediatric patients with acute lymphoblastic leukemia treated with total body irradiation-free allogeneic hematopoietic stem cell transplantation&#58; comparison of patients with and without central nervous system involvement"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "A&#46;A&#46; Hamidieh"
                            1 => "S&#46;M&#46; Monzavi"
                            2 => "M&#46; Kaboutari"
                            3 => "M&#46; Behfar"
                            4 => "M&#46; Esfandbod"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.bbmt.2017.08.036"
                      "Revista" => array:6 [
                        "tituloSerie" => "Biol Blood Marrow Transplant"
                        "fecha" => "2017"
                        "volumen" => "23"
                        "paginaInicial" => "2110"
                        "paginaFinal" => "2117"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28870778"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0420"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Reduced-intensity versus conventional myeloablative conditioning allogeneic stem cell transplantation for patients with acute lymphoblastic leukemia&#58; a retrospective study from the European Group for Blood and Marrow Transplantation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Mohty"
                            1 => "M&#46; Labopin"
                            2 => "L&#46; Volin"
                            3 => "A&#46; Gratwohl"
                            4 => "G&#46; Soci&#233;"
                            5 => "J&#46; Esteve"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1182/blood-2010-02-266551"
                      "Revista" => array:6 [
                        "tituloSerie" => "Blood"
                        "fecha" => "2010"
                        "volumen" => "116"
                        "paginaInicial" => "4439"
                        "paginaFinal" => "4443"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20716774"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0425"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The outcome of full-intensity and reduced-intensity conditioning matched sibling or unrelated donor transplantation in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first and second complete remission"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46;I&#46; Marks"
                            1 => "T&#46; Wang"
                            2 => "W&#46;S&#46; P&#233;rez"
                            3 => "J&#46;H&#46; Antin"
                            4 => "E&#46; Copelan"
                            5 => "R&#46;P&#46; Gale"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1182/blood-2010-01-264077"
                      "Revista" => array:6 [
                        "tituloSerie" => "Blood"
                        "fecha" => "2010"
                        "volumen" => "116"
                        "paginaInicial" => "366"
                        "paginaFinal" => "374"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20404137"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0430"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Impact of transplant eligibility and availability of a human leukocyte antigen-identical matched related donor on outcome of older patients with acute lymphoblastic leukemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46; Barba"
                            1 => "R&#46; Martino"
                            2 => "D&#46; Martinez-Cuadron"
                            3 => "G&#46; Olga"
                            4 => "A&#46; Esquirol"
                            5 => "C&#46; Gil-Cort&#233;s"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3109/10428194.2015.1014365"
                      "Revista" => array:6 [
                        "tituloSerie" => "Leuk Lymphoma"
                        "fecha" => "2015"
                        "volumen" => "56"
                        "paginaInicial" => "2812"
                        "paginaFinal" => "2818"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25686647"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0435"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Reduced-intensity conditioning regimens for allogeneic transplantation in children with acute lymphoblastic leukemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;R&#46; Verneris"
                            1 => "M&#46; Eapen"
                            2 => "R&#46; Duerst"
                            3 => "P&#46;A&#46; Carpenter"
                            4 => "M&#46;J&#46; Burke"
                            5 => "B&#46;V&#46; Afanasyev"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.bbmt.2010.03.009"
                      "Revista" => array:6 [
                        "tituloSerie" => "Biol Blood Marrow Transplant"
                        "fecha" => "2010"
                        "volumen" => "16"
                        "paginaInicial" => "1237"
                        "paginaFinal" => "1244"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20302960"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0440"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "H&#46;M&#46; Kantarjian"
                            1 => "D&#46;J&#46; DeAngelo"
                            2 => "M&#46; Stelljes"
                            3 => "G&#46; Martinelli"
                            4 => "M&#46; Liedtke"
                            5 => "W&#46; Stock"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1509277"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2016"
                        "volumen" => "375"
                        "paginaInicial" => "740"
                        "paginaFinal" => "753"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27292104"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0445"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatic adverse event profile of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukaemia&#58; results from the open-label&#44; randomised&#44; phase 3 INO-VATE study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "H&#46;M&#46; Kantarjian"
                            1 => "D&#46;J&#46; DeAngelo"
                            2 => "A&#46;S&#46; Advani"
                            3 => "M&#46; Stelljes"
                            4 => "P&#46; Kebriaei"
                            5 => "R&#46;D&#46; Cassaday"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S2352-3026(17)30103-5"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet Haematol"
                        "fecha" => "2017"
                        "volumen" => "4"
                        "paginaInicial" => "e387"
                        "paginaFinal" => "e398"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28687420"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0450"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Defibrotide for prophylaxis of hepatic veno-occlusive disease in paediatric haemopoietic stem-cell transplantation&#58; an open-label&#44; phase 3&#44; randomised controlled trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Corbacioglu"
                            1 => "S&#46; Cesaro"
                            2 => "M&#46; Faraci"
                            3 => "D&#46; Valteau-Couanet"
                            4 => "B&#46; Gruhn"
                            5 => "A&#46; Rovelli"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(11)61938-7"
                      "Revista" => array:7 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2012"
                        "volumen" => "379"
                        "paginaInicial" => "1301"
                        "paginaFinal" => "1309"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22364685"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S1933287417300648"
                          "estado" => "S300"
                          "issn" => "19332874"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0455"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "More chronic GvHD and non-relapse mortality after peripheral blood stem cell compared with bone marrow in hematopoietic transplantation for paediatric acute lymphoblastic leukemia&#58; a retrospective study on behalf of the EBMT Paediatric Diseases Working Party"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Simonin"
                            1 => "A&#46; Dalissier"
                            2 => "M&#46; Labopin"
                            3 => "A&#46; Willasch"
                            4 => "M&#46; Zecca"
                            5 => "A&#46; Mouhab"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/bmt.2017.66"
                      "Revista" => array:6 [
                        "tituloSerie" => "Bone Marrow Transplant"
                        "fecha" => "2017"
                        "volumen" => "52"
                        "paginaInicial" => "1071"
                        "paginaFinal" => "1073"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28394370"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0460"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cord blood transplantation&#58; state of the art"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "E&#46; Gluckman"
                            1 => "V&#46; Rocha"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3324/haematol.2009.005694"
                      "Revista" => array:7 [
                        "tituloSerie" => "Haematologica"
                        "fecha" => "2009"
                        "volumen" => "94"
                        "paginaInicial" => "451"
                        "paginaFinal" => "454"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19336748"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0140673607617784"
                          "estado" => "S300"
                          "issn" => "01406736"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0465"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia&#58; a comparison study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Eapen"
                            1 => "P&#46; Rubinstein"
                            2 => "M&#46;J&#46; Zhang"
                            3 => "C&#46; Stevens"
                            4 => "J&#46; Kurtzberg"
                            5 => "A&#46; Scaradavou"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(07)60915-5"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2007"
                        "volumen" => "369"
                        "paginaInicial" => "1947"
                        "paginaFinal" => "1954"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17560447"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0470"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Umbilical cord blood transplantation from unrelated donors in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;L&#46; Pi&#241;ana"
                            1 => "J&#46; Sanz"
                            2 => "A&#46; Picardi"
                            3 => "C&#46; Ferr&#225;"
                            4 => "R&#46; Martino"
                            5 => "P&#46; Barba"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3324/haematol.2013.091009"
                      "Revista" => array:6 [
                        "tituloSerie" => "Haematologica"
                        "fecha" => "2014"
                        "volumen" => "99"
                        "paginaInicial" => "378"
                        "paginaFinal" => "384"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24097633"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0475"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Is the use of unrelated donor transplantation leveling off in Europe&#63; The 2016 European Society for Blood and Marrow Transplant activity survey report"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;R&#46; Passweg"
                            1 => "H&#46; Baldomero"
                            2 => "P&#46; Bader"
                            3 => "G&#46;W&#46; Basak"
                            4 => "C&#46; Bonini"
                            5 => "R&#46; Duarte"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/s41409-018-0153-1"
                      "Revista" => array:6 [
                        "tituloSerie" => "Bone Marrow Transplant"
                        "fecha" => "2018"
                        "volumen" => "53"
                        "paginaInicial" => "1139"
                        "paginaFinal" => "1148"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29540849"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0480"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Haploidentical transplantation with post-transplantation cyclophosphamide for high-risk acute lymphoblastic leukemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46;A&#46; Srour"
                            1 => "D&#46;R&#46; Milton"
                            2 => "A&#46; Bashey"
                            3 => "A&#46; Karduss-Urueta"
                            4 => "M&#46;M&#46; al Malki"
                            5 => "R&#46; Romee"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.bbmt.2016.11.008"
                      "Revista" => array:6 [
                        "tituloSerie" => "Biol Blood Marrow Transplant"
                        "fecha" => "2017"
                        "volumen" => "23"
                        "paginaInicial" => "318"
                        "paginaFinal" => "324"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27856368"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0485"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "&#947;&#948; T-cell reconstitution after HLA-haploidentical hematopoietic transplantation depleted of TCR-&#945;&#946;&#43;&#47;CD19&#43; lymphocytes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "I&#46; Airoldi"
                            1 => "A&#46; Bertaina"
                            2 => "I&#46; Prigione"
                            3 => "A&#46; Zorzoli"
                            4 => "D&#46; Pagliara"
                            5 => "C&#46; Cocco"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1182/blood-2014-09-599423"
                      "Revista" => array:6 [
                        "tituloSerie" => "Blood"
                        "fecha" => "2015"
                        "volumen" => "125"
                        "paginaInicial" => "2349"
                        "paginaFinal" => "2358"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25612623"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0490"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treatment of young patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia using increased dose of imatinib and deintensified chemotherapy before allogeneic stem cell transplantation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;M&#46; Ribera"
                            1 => "O&#46; Garc&#237;a"
                            2 => "P&#46; Montesinos"
                            3 => "S&#46; Brunet"
                            4 => "E&#46; Abella"
                            5 => "M&#46; Barrios"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2141.2012.09240.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Haematol"
                        "fecha" => "2012"
                        "volumen" => "159"
                        "paginaInicial" => "78"
                        "paginaFinal" => "81"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22823211"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0495"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Chemotherapy-phased imatinib pulses improve long-term outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia&#58; Northern Italy Leukemia Group protocol 09&#47;00"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46; Bassan"
                            1 => "G&#46; Rossi"
                            2 => "E&#46;M&#46; Pogliani"
                            3 => "E&#46; di Bona"
                            4 => "E&#46; Angelucci"
                            5 => "I&#46; Cavattoni"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2010.28.1287"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2010"
                        "volumen" => "28"
                        "paginaInicial" => "3644"
                        "paginaFinal" => "3652"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20606084"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0500"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Achieving molecular remission before allogeneic stem cell transplantation in adult patients with philadelphia chromosome-positive acute lymphoblastic leukemia&#58; impact on relapse and long-term outcome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46; Lussana"
                            1 => "T&#46; Intermesoli"
                            2 => "F&#46; Gianni"
                            3 => "C&#46; Boschini"
                            4 => "A&#46; Masciulli"
                            5 => "O&#46; Spinelli"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.bbmt.2016.07.021"
                      "Revista" => array:6 [
                        "tituloSerie" => "Biol Blood Marrow Transplant"
                        "fecha" => "2016"
                        "volumen" => "22"
                        "paginaInicial" => "1983"
                        "paginaFinal" => "1987"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27492792"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib0505"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Impact of MRD and TKI on allogeneic hematopoietic cell transplantation for Ph&#43; ALL&#58; a study from the adult ALL WG of the JSHCT"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Nishiwaki"
                            1 => "K&#46; Imai"
                            2 => "S&#46; Mizuta"
                            3 => "H&#46; Kanamori"
                            4 => "K&#46; Ohashi"
                            5 => "T&#46; Fukuda"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/bmt.2015.217"
                      "Revista" => array:6 [
                        "tituloSerie" => "Bone Marrow Transplant"
                        "fecha" => "2016"
                        "volumen" => "51"
                        "paginaInicial" => "43"
                        "paginaFinal" => "50"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26389833"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib0510"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long-term follow-up of the imatinib GRAAPH-2003 study in newly diagnosed patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia&#58; a GRAALL study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Tanguy-Schmidt"
                            1 => "P&#46; Rousselot"
                            2 => "Y&#46; Chalandon"
                            3 => "J&#46;M&#46; Cayuela"
                            4 => "S&#46; Hayette"
                            5 => "M&#46;C&#46; Vekemans"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.bbmt.2012.08.021"
                      "Revista" => array:6 [
                        "tituloSerie" => "Biol Blood Marrow Transplant"
                        "fecha" => "2013"
                        "volumen" => "19"
                        "paginaInicial" => "150"
                        "paginaFinal" => "155"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22960387"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib0515"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Complete hematologic and molecular response in adult patients with relapsed&#47;refractory Philadelphia chromosome-positive B-precursor acute lymphoblastic leukemia following treatment with blinatumomab&#58; results from a phase II&#44; single-arm&#44; multicenter study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46; Martinelli"
                            1 => "N&#46; Boissel"
                            2 => "P&#46; Chevallier"
                            3 => "O&#46; Ottmann"
                            4 => "N&#46; G&#246;kbuget"
                            5 => "M&#46;S&#46; Topp"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2016.69.3531"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2017"
                        "volumen" => "35"
                        "paginaInicial" => "1795"
                        "paginaFinal" => "1802"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28355115"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0520"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Longer follow-up confirms major improvement in outcome in children and adolescents with Philadelphia chromosome acute lymphoblastic leukaemia treated with continuous imatinib and haematopoietic stem cell transplantation&#46; Results from the Spanish Cooperative Study SHOP&#47;ALL-2005"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Rives"
                            1 => "M&#46; Cam&#243;s"
                            2 => "J&#46; Estella"
                            3 => "P&#46; G&#243;mez"
                            4 => "M&#46;J&#46; Moreno"
                            5 => "J&#46;L&#46; Vivanco"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/bjh.12373"
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Haematol"
                        "fecha" => "2013"
                        "volumen" => "162"
                        "paginaInicial" => "419"
                        "paginaFinal" => "421"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23668628"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib0525"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Imatinib after induction for treatment of children and adolescents with Philadelphia-chromosome-positive acute lymphoblastic leukaemia &#40;EsPhALL&#41;&#58; a randomised&#44; open-label&#44; intergroup study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Biondi"
                            1 => "M&#46; Schrappe"
                            2 => "P&#46; de Lorenzo"
                            3 => "A&#46; Castor"
                            4 => "G&#46; Lucchini"
                            5 => "V&#46; Gandemer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S1470-2045(12)70377-7"
                      "Revista" => array:7 [
                        "tituloSerie" => "Lancet Oncol"
                        "fecha" => "2012"
                        "volumen" => "13"
                        "paginaInicial" => "936"
                        "paginaFinal" => "945"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22898679"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0140673616310121"
                          "estado" => "S300"
                          "issn" => "01406736"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib0530"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;H&#46; Park"
                            1 => "I&#46; Rivi&#232;re"
                            2 => "M&#46; Gonen"
                            3 => "X&#46; Wang"
                            4 => "B&#46; S&#233;n&#233;chal"
                            5 => "K&#46;J&#46; Curran"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1709919"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2018"
                        "volumen" => "378"
                        "paginaInicial" => "449"
                        "paginaFinal" => "459"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29385376"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib0535"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inotuzumab ozogamicin in combination with low-intensity chemotherapy for older patients with Philadelphia chromosome-negative acute lymphoblastic leukaemia&#58; a single-arm&#44; phase 2 study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "H&#46; Kantarjian"
                            1 => "F&#46; Ravandi"
                            2 => "N&#46;J&#46; Short"
                            3 => "X&#46; Huang"
                            4 => "N&#46; Jain"
                            5 => "K&#46; Sasaki"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S1470-2045(18)30011-1"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet Oncol"
                        "fecha" => "2018"
                        "volumen" => "19"
                        "paginaInicial" => "240"
                        "paginaFinal" => "248"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29352703"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib0540"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Impact of minimal residual disease&#44; detected by flow cytometry&#44; on outcome of myeloablative hematopoietic cell transplantation for acute lymphoblastic leukemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Bar"
                            1 => "B&#46;L&#46; Wood"
                            2 => "J&#46;P&#46; Radich"
                            3 => "K&#46;C&#46; Doney"
                            4 => "A&#46;E&#46; Woolfrey"
                            5 => "C&#46; Delaney"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1155/2014/421723"
                      "Revista" => array:5 [
                        "tituloSerie" => "Leuk Res Treatment"
                        "fecha" => "2014"
                        "volumen" => "2014"
                        "paginaInicial" => "421723"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24778882"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib0545"
              "etiqueta" => "49"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The effect of peritransplant minimal residual disease in adults with acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Y&#46; Zhou"
                            1 => "R&#46; Slack"
                            2 => "J&#46;L&#46; Jorgensen"
                            3 => "S&#46;A&#46; Wang"
                            4 => "G&#46; Rondon"
                            5 => "M&#46; de Lima"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.clml.2014.01.002"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Lymphoma Myeloma Leuk"
                        "fecha" => "2014"
                        "volumen" => "14"
                        "paginaInicial" => "319"
                        "paginaFinal" => "326"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24548609"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib0550"
              "etiqueta" => "50"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Dh&#233;din"
                            1 => "A&#46; Huynh"
                            2 => "S&#46; Maury"
                            3 => "R&#46; Tabrizi"
                            4 => "K&#46; Beldjord"
                            5 => "V&#46; Asnafi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1182/blood-2014-09-599894"
                      "Revista" => array:6 [
                        "tituloSerie" => "Blood"
                        "fecha" => "2015"
                        "volumen" => "125"
                        "paginaInicial" => "2486"
                        "paginaFinal" => "2496"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25587040"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            50 => array:3 [
              "identificador" => "bib0555"
              "etiqueta" => "51"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Relationship between minimal residual disease measured by multiparametric flow cytometry prior to allogeneic hematopoietic stem cell transplantation and outcome in children with acute lymphoblastic leukemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "I&#46; Elorza"
                            1 => "C&#46; Palacio"
                            2 => "J&#46;L&#46; Dapena"
                            3 => "L&#46; Gallur"
                            4 => "J&#46; S&#225;nchez de Toledo"
                            5 => "C&#46; D&#237;az de Heredia"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3324/haematol.2009.010843"
                      "Revista" => array:7 [
                        "tituloSerie" => "Haematologica"
                        "fecha" => "2010"
                        "volumen" => "95"
                        "paginaInicial" => "936"
                        "paginaFinal" => "941"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20179088"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S2213858717304163"
                          "estado" => "S300"
                          "issn" => "22138587"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            51 => array:3 [
              "identificador" => "bib0560"
              "etiqueta" => "52"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; G&#246;kbuget"
                            1 => "H&#46; Dombret"
                            2 => "M&#46; Bonifacio"
                            3 => "A&#46; Reichle"
                            4 => "C&#46; Graux"
                            5 => "C&#46; Faul"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Blood"
                        "fecha" => "2018"
                        "volumen" => "13"
                        "paginaInicial" => "1522"
                        "paginaFinal" => "1531"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            52 => array:3 [
              "identificador" => "bib0565"
              "etiqueta" => "53"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46;L&#46; Maude"
                            1 => "T&#46;W&#46; Laetsch"
                            2 => "J&#46; Buechner"
                            3 => "S&#46; Rives"
                            4 => "M&#46; Boyer"
                            5 => "H&#46; Bittencourt"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1709866"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2018"
                        "volumen" => "378"
                        "paginaInicial" => "439"
                        "paginaFinal" => "448"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29385370"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            53 => array:3 [
              "identificador" => "bib0570"
              "etiqueta" => "54"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Monitoring of minimal residual disease after allogeneic stem-cell transplantation in relapsed childhood acute lymphoblastic leukemia allows for the identification of impending relapse&#58; results of the ALL-BFM-SCT 2003 trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46; Bader"
                            1 => "H&#46; Kreyenberg"
                            2 => "A&#46; von Stackelberg"
                            3 => "C&#46; Eckert"
                            4 => "E&#46; Salzmann-Manrique"
                            5 => "R&#46; Meisel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2014.58.4631"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2015"
                        "volumen" => "33"
                        "paginaInicial" => "1275"
                        "paginaFinal" => "1284"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25605857"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S1933287415003670"
                          "estado" => "S300"
                          "issn" => "19332874"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            54 => array:3 [
              "identificador" => "bib0575"
              "etiqueta" => "55"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Increasing mixed chimerism is an important prognostic factor for unfavorable outcome in children with acute lymphoblastic leukemia after allogeneic stem-cell transplantation&#58; possible role for pre-emptive immunotherapy&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46; Bader"
                            1 => "H&#46; Kreyenberg"
                            2 => "W&#46; Hoelle"
                            3 => "G&#46; Dueckers"
                            4 => "R&#46; Handgretinger"
                            5 => "P&#46; Lang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2004.05.198"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2004"
                        "volumen" => "22"
                        "paginaInicial" => "1696"
                        "paginaFinal" => "1705"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15117992"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            55 => array:3 [
              "identificador" => "bib0580"
              "etiqueta" => "56"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Outcome of relapse after allogeneic HSCT in children with ALL enrolled in the ALL-SCT 2003&#47;2007 trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Kuhlen"
                            1 => "A&#46;M&#46; Willasch"
                            2 => "J&#46;H&#46; Dalle"
                            3 => "J&#46; Wachowiak"
                            4 => "I&#46; Yaniv"
                            5 => "M&#46; Ifversen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/bjh.14965"
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Haematol"
                        "fecha" => "2018"
                        "volumen" => "180"
                        "paginaInicial" => "82"
                        "paginaFinal" => "89"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29193007"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            56 => array:3 [
              "identificador" => "bib0585"
              "etiqueta" => "57"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Second hematopoietic stem cell transplantation for post-transplantation relapsed acute leukemia in children&#58; a retrospective EBMT-PDWP study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "I&#46; Yaniv"
                            1 => "A&#46;C&#46; Krauss"
                            2 => "E&#46; Beohou"
                            3 => "A&#46; Dalissier"
                            4 => "S&#46; Corbacioglu"
                            5 => "M&#46; Zecca"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.bbmt.2018.03.002"
                      "Revista" => array:6 [
                        "tituloSerie" => "Biol Blood Marrow Transplant"
                        "fecha" => "2018"
                        "volumen" => "24"
                        "paginaInicial" => "1629"
                        "paginaFinal" => "131642"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29548831"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            57 => array:3 [
              "identificador" => "bib0590"
              "etiqueta" => "58"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "H&#46; Kantarjian"
                            1 => "A&#46; Stein"
                            2 => "N&#46; G&#246;kbuget"
                            3 => "A&#46;K&#46; Fielding"
                            4 => "A&#46;C&#46; Schuh"
                            5 => "J&#46;M&#46; Ribera"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1609783"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2017"
                        "volumen" => "376"
                        "paginaInicial" => "836"
                        "paginaFinal" => "847"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28249141"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            58 => array:3 [
              "identificador" => "bib0595"
              "etiqueta" => "59"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Chimeric antigen receptor T cells for sustained remissions in leukemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46;L&#46; Maude"
                            1 => "N&#46; Frey"
                            2 => "P&#46;A&#46; Shaw"
                            3 => "R&#46; Aplenc"
                            4 => "D&#46;M&#46; Barrett"
                            5 => "N&#46;J&#46; Bunin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1407222"
                      "Revista" => array:7 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2014"
                        "volumen" => "371"
                        "paginaInicial" => "1507"
                        "paginaFinal" => "1517"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25317870"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0140673609600404"
                          "estado" => "S300"
                          "issn" => "01406736"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            59 => array:3 [
              "identificador" => "bib0600"
              "etiqueta" => "60"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inotuzumab ozogamicin&#44; an anti-CD22-calecheamicin conjugate&#44; for refractory and relapsed acute lymphocytic leukaemia&#58; a phase 2 study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "H&#46; Kantarjian"
                            1 => "D&#46; Thomas"
                            2 => "J&#46; Jorgensen"
                            3 => "E&#46; Jabbour"
                            4 => "P&#46; Kebriaei"
                            5 => "M&#46; Rytting"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S1470-2045(11)70386-2"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet Oncol"
                        "fecha" => "2012"
                        "volumen" => "13"
                        "paginaInicial" => "403"
                        "paginaFinal" => "411"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22357140"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/23870206/0000015300000001/v1_201906260821/S238702061930275X/v1_201906260821/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "44147"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Review"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015300000001/v1_201906260821/S238702061930275X/v1_201906260821/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S238702061930275X?idApp=UINPBA00004N"
]